CA2963322A1 - Methods and compositions of neuregulins for preventing, treating or delaying preserved ejection fraction cardiac failure - Google Patents
Methods and compositions of neuregulins for preventing, treating or delaying preserved ejection fraction cardiac failure Download PDFInfo
- Publication number
- CA2963322A1 CA2963322A1 CA2963322A CA2963322A CA2963322A1 CA 2963322 A1 CA2963322 A1 CA 2963322A1 CA 2963322 A CA2963322 A CA 2963322A CA 2963322 A CA2963322 A CA 2963322A CA 2963322 A1 CA2963322 A1 CA 2963322A1
- Authority
- CA
- Canada
- Prior art keywords
- heart failure
- ejection fraction
- nrg
- preserved ejection
- neuregulin
- 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.)
- Abandoned
Links
- 108050003475 Neuregulin Proteins 0.000 title claims abstract description 50
- 102000014413 Neuregulin Human genes 0.000 title claims abstract description 49
- 239000000203 mixture Substances 0.000 title claims description 5
- 206010019280 Heart failures Diseases 0.000 title abstract description 29
- 238000000034 method Methods 0.000 title abstract description 15
- 241000124008 Mammalia Species 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 16
- 208000038003 heart failure with preserved ejection fraction Diseases 0.000 claims description 40
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 9
- 102100040896 Growth/differentiation factor 15 Human genes 0.000 claims description 6
- 101000893549 Homo sapiens Growth/differentiation factor 15 Proteins 0.000 claims description 6
- 101000653754 Rattus norvegicus Sphingosine 1-phosphate receptor 5 Proteins 0.000 claims description 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 201000010099 disease Diseases 0.000 abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 230000002861 ventricular Effects 0.000 description 33
- 238000011282 treatment Methods 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 21
- 206010020772 Hypertension Diseases 0.000 description 19
- 206010007559 Cardiac failure congestive Diseases 0.000 description 17
- 241000700159 Rattus Species 0.000 description 17
- 230000003205 diastolic effect Effects 0.000 description 17
- 208000003037 Diastolic Heart Failure Diseases 0.000 description 16
- 230000002107 myocardial effect Effects 0.000 description 14
- 102000012545 EGF-like domains Human genes 0.000 description 13
- 108050002150 EGF-like domains Proteins 0.000 description 13
- 230000006870 function Effects 0.000 description 13
- 230000001631 hypertensive effect Effects 0.000 description 13
- 210000002216 heart Anatomy 0.000 description 12
- 230000004217 heart function Effects 0.000 description 12
- 230000003247 decreasing effect Effects 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 150000001413 amino acids Chemical group 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 208000008253 Systolic Heart Failure Diseases 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 7
- 229960000830 captopril Drugs 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 230000000004 hemodynamic effect Effects 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 102000001301 EGF receptor Human genes 0.000 description 6
- 108060006698 EGF receptor Proteins 0.000 description 6
- 108090000556 Neuregulin-1 Proteins 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000001771 impaired effect Effects 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- 238000002592 echocardiography Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 210000004115 mitral valve Anatomy 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 102400000058 Neuregulin-1 Human genes 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 238000011265 2D-echocardiography Methods 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 102100031968 Ephrin type-B receptor 2 Human genes 0.000 description 3
- 102000048238 Neuregulin-1 Human genes 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 238000005265 energy consumption Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 210000004897 n-terminal region Anatomy 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 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 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 102000008873 Angiotensin II receptor Human genes 0.000 description 2
- 108050000824 Angiotensin II receptor Proteins 0.000 description 2
- 206010007558 Cardiac failure chronic Diseases 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 206010020880 Hypertrophy Diseases 0.000 description 2
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000029578 Muscle disease Diseases 0.000 description 2
- 102400000057 Neuregulin-2 Human genes 0.000 description 2
- 101800000675 Neuregulin-2 Proteins 0.000 description 2
- 102400000054 Neuregulin-3 Human genes 0.000 description 2
- 101800000673 Neuregulin-3 Proteins 0.000 description 2
- 101800002641 Neuregulin-4 Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 2
- 208000032023 Signs and Symptoms Diseases 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 210000004413 cardiac myocyte Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 229940030606 diuretics Drugs 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 206010020871 hypertrophic cardiomyopathy Diseases 0.000 description 2
- 210000005246 left atrium Anatomy 0.000 description 2
- 210000005240 left ventricle Anatomy 0.000 description 2
- 239000008176 lyophilized powder Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000036454 renin-angiotensin system Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000002235 sarcomere Anatomy 0.000 description 2
- 230000008054 signal transmission Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- HMRWQTHUDVXMGH-GUBZILKMSA-N Ala-Glu-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN HMRWQTHUDVXMGH-GUBZILKMSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- BSGXXYRIDXUEOM-IHRRRGAJSA-N Cys-Phe-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CS)N BSGXXYRIDXUEOM-IHRRRGAJSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010052337 Diastolic dysfunction Diseases 0.000 description 1
- 206010013971 Dyspnoea exertional Diseases 0.000 description 1
- 206010013974 Dyspnoea paroxysmal nocturnal Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000056372 ErbB-3 Receptor Human genes 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- QDMVXRNLOPTPIE-WDCWCFNPSA-N Glu-Lys-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QDMVXRNLOPTPIE-WDCWCFNPSA-N 0.000 description 1
- GDOZQTNZPCUARW-YFKPBYRVSA-N Gly-Gly-Glu Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O GDOZQTNZPCUARW-YFKPBYRVSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 101001109792 Homo sapiens Pro-neuregulin-2, membrane-bound isoform Proteins 0.000 description 1
- 101001109765 Homo sapiens Pro-neuregulin-3, membrane-bound isoform Proteins 0.000 description 1
- 101001109767 Homo sapiens Pro-neuregulin-4, membrane-bound isoform Proteins 0.000 description 1
- 206010058558 Hypoperfusion Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 206010067286 Left atrial dilatation Diseases 0.000 description 1
- KZZCOWMDDXDKSS-CIUDSAMLSA-N Leu-Ser-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KZZCOWMDDXDKSS-CIUDSAMLSA-N 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 102400000055 Neuregulin-4 Human genes 0.000 description 1
- 206010030124 Oedema peripheral Diseases 0.000 description 1
- 208000004327 Paroxysmal Dyspnea Diseases 0.000 description 1
- 208000025584 Pericardial disease Diseases 0.000 description 1
- OWCLJDXHHZUNEL-IHRRRGAJSA-N Phe-Cys-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O OWCLJDXHHZUNEL-IHRRRGAJSA-N 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102100022668 Pro-neuregulin-2, membrane-bound isoform Human genes 0.000 description 1
- 102100022659 Pro-neuregulin-3, membrane-bound isoform Human genes 0.000 description 1
- 102100022658 Pro-neuregulin-4, membrane-bound isoform Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010071436 Systolic dysfunction Diseases 0.000 description 1
- KTEZUXISLQTDDQ-NHCYSSNCSA-N Val-Lys-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)O)N KTEZUXISLQTDDQ-NHCYSSNCSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 206010002906 aortic stenosis Diseases 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 108010077245 asparaginyl-proline Proteins 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000001174 endocardium Anatomy 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 238000001595 flow curve Methods 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 230000010005 growth-factor like effect Effects 0.000 description 1
- 230000009067 heart development Effects 0.000 description 1
- 208000018578 heart valve disease Diseases 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 210000004692 intercellular junction Anatomy 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 108010009298 lysylglutamic acid Proteins 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000004220 muscle function Effects 0.000 description 1
- 230000010117 myocardial relaxation Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000004088 pulmonary circulation Effects 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229940124629 β-receptor antagonist Drugs 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410550212.7A CN105561298A (zh) | 2014-10-17 | 2014-10-17 | 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 |
| CN201410550212.7 | 2014-10-17 | ||
| PCT/CN2015/091459 WO2016058493A1 (zh) | 2014-10-17 | 2015-10-08 | 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2963322A1 true CA2963322A1 (en) | 2016-04-21 |
Family
ID=55746124
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2963322A Abandoned CA2963322A1 (en) | 2014-10-17 | 2015-10-08 | Methods and compositions of neuregulins for preventing, treating or delaying preserved ejection fraction cardiac failure |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US10561709B2 (enExample) |
| EP (2) | EP3207940B1 (enExample) |
| JP (4) | JP2017532343A (enExample) |
| KR (2) | KR102603711B1 (enExample) |
| CN (3) | CN105561298A (enExample) |
| AU (2) | AU2015333335B2 (enExample) |
| CA (1) | CA2963322A1 (enExample) |
| ES (1) | ES2924395T3 (enExample) |
| RU (1) | RU2017116973A (enExample) |
| WO (1) | WO2016058493A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111407881A (zh) * | 2019-01-07 | 2020-07-14 | 上海泽生科技开发股份有限公司 | 神经调节蛋白用于预防、治疗或延迟心肌损伤的方法和组合物 |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0620819A2 (pt) | 2005-12-30 | 2011-11-22 | Zensun Shangai Science & Technology Ltd | uso de uma neuregulina (nrg) de liberação prolongada, nrg em uma liberação prolongada de uma dosagem baixa constante, e, composição de liberação prolongada para prevenir, tratar ou retardar uma doença ou distúrbio em um mamìfero |
| JP6096262B2 (ja) | 2009-08-25 | 2017-03-15 | ゼンサン （シャンハイ） サイエンス アンド テクノロジー，シーオー．，エルティーディー． | ニューレグリンに基づく心不全の治療方法 |
| CN102139095A (zh) | 2010-01-29 | 2011-08-03 | 上海泽生科技开发有限公司 | 神经调节蛋白用于预防、治疗或延迟心脏缺血再灌注损伤的方法和组合物 |
| WO2013053076A1 (en) | 2011-10-10 | 2013-04-18 | Zensun （Shanghai）Science & Technology Limited | Compositions and methods for treating heart failure |
| JP6475623B2 (ja) | 2012-10-08 | 2019-02-27 | ゼンスン（シャンハイ）サイエンス アンド テクノロジー カンパニー リミテッド | 糖尿病患者における心不全の治療用組成物 |
| CA2911848A1 (en) | 2013-05-22 | 2014-11-27 | Zensun (Shanghai) Science & Technology, Ltd. | Extended release of neuregulin for treating heart failure |
| CN110946993A (zh) | 2014-01-03 | 2020-04-03 | 上海泽生科技开发股份有限公司 | 纽兰格林制剂的配方 |
| CN105497876B (zh) | 2014-09-24 | 2021-01-15 | 上海泽生科技开发股份有限公司 | 神经调节蛋白用于预防、治疗或延迟心脏室性心律失常的方法和组合物 |
| JP7575272B2 (ja) * | 2018-04-11 | 2024-10-29 | サルブリス バイオセラピューティクス，インコーポレイティド | ヒトニューレグリン－１（ｎｒｇ－１）組換え型融合タンパク質組成物及びその使用方法 |
| AR121035A1 (es) | 2019-04-01 | 2022-04-13 | Lilly Co Eli | Compuestos de neuregulina-4 y métodos de uso |
| CN113289002A (zh) * | 2020-02-24 | 2021-08-24 | 上海泽生科技开发股份有限公司 | 神经调节蛋白用于预防、治疗或延缓心力衰竭的方法和组合物 |
| CN116710139A (zh) * | 2020-11-12 | 2023-09-05 | 安进股份有限公司 | 通过施用奥美卡替莫卡必尔治疗心力衰竭的方法 |
| CN117797243A (zh) * | 2022-09-30 | 2024-04-02 | 上海泽生科技开发股份有限公司 | 神经调节蛋白及其应用 |
Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989001489A1 (en) | 1987-08-10 | 1989-02-23 | Commonwealth Scientific And Industrial Research Or | Control of angiogenesis and compositions and methods therefor |
| US5530109A (en) | 1991-04-10 | 1996-06-25 | Ludwig Institute For Cancer Research | DNA encoding glial mitogenic factors |
| 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 |
| US5834229A (en) | 1991-05-24 | 1998-11-10 | Genentech, Inc. | Nucleic acids vectors and host cells encoding and expressing heregulin 2-α |
| US6750196B1 (en) | 1995-03-27 | 2004-06-15 | Acorda Therapeutics | Methods of treating disorders of the eye |
| US5912326A (en) | 1995-09-08 | 1999-06-15 | President And Fellows Of Harvard College | Cerebellum-derived growth factors |
| IL130827A0 (en) | 1997-02-10 | 2001-01-28 | Genentech Inc | Heregulin variants |
| CA2306228A1 (en) | 1997-10-14 | 1999-04-22 | Cambridge Neuroscience, Inc. | Therapeutic methods comprising use of a neuregulin |
| US6054261A (en) | 1998-05-20 | 2000-04-25 | Q-Pharma, Inc. | Coenzyme Q10 compositions for organ protection during perfusion |
| 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 |
| AUPQ105799A0 (en) | 1999-06-18 | 1999-07-08 | Victor Chang Cardiac Research Institute, The | Cell growth inhibition |
| WO2001064877A2 (en) | 2000-02-28 | 2001-09-07 | Decode Genetics Ehf | Human schizophrenia gene |
| AU2001274947B2 (en) | 2000-05-23 | 2006-08-17 | Acorda Therapeutics, Inc. | Nrg-2 nucleic acid molecules, polypeptides, and diagnostic and therapeutic methods |
| WO2002024889A2 (en) | 2000-09-12 | 2002-03-28 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Optimized cardiac contraction through differential phosphorylation of myosin |
| US6482624B2 (en) | 2000-11-14 | 2002-11-19 | Pe Corporation (Ny) | Isolated human kinase proteins, nucleic acid molecules encoding human kinase proteins, and uses thereof |
| RU2180843C1 (ru) | 2001-02-19 | 2002-03-27 | Новокузнецкий государственный институт усовершенствования врачей | Способ профилактики повторного инфаркта миокарда |
| CN1498656A (zh) | 2002-11-08 | 2004-05-26 | 上海泽生科技开发有限公司 | 神经调节蛋白用于心肌梗死治疗的方法和组合物 |
| WO2003099320A1 (en) | 2002-05-24 | 2003-12-04 | Zensun (Shanghai) Sci-Tech.Ltd | Neuregulin based methods and compositions for treating viral myocarditis and dilated cardiomyopathy |
| US20060275770A1 (en) | 2002-11-27 | 2006-12-07 | Daniel Bednarik | Heart failure gene determination and therapeutic screening |
| MXPA05012619A (es) | 2003-05-21 | 2006-02-08 | Univ Texas | Inhibicion de la proteina cinasa c-mu como un tratamiento para la hipertrofia cardiaca y la falla cardiaca. |
| CN1715926B (zh) | 2004-07-02 | 2011-08-17 | 上海泽生科技开发有限公司 | 神经调节蛋白突变体的应用 |
| US20080213395A1 (en) | 2004-10-14 | 2008-09-04 | Adventures Plus Pty Ltd | Method for the Treatment of Gastrointestinal and Other Disorders with an Admixture of Vitamins |
| US20060160062A1 (en) | 2005-01-14 | 2006-07-20 | Young Lindon H | Perfusion and/or preservation solution for organs |
| US20070141548A1 (en) | 2005-03-11 | 2007-06-21 | Jorg Kohl | Organ transplant solutions and method for transplanting organs |
| CN100361709C (zh) | 2005-08-30 | 2008-01-16 | 山东省生物药物研究院 | 一种对生命活性物质有保护作用的糖类组合 |
| CN1768859A (zh) | 2005-10-24 | 2006-05-10 | 天津大学 | 基于醛基的微粒表面多重生物功能因子组装方法 |
| US20070213264A1 (en) | 2005-12-02 | 2007-09-13 | Mingdong Zhou | Neuregulin variants and methods of screening and using thereof |
| CN101394861A (zh) * | 2005-12-30 | 2009-03-25 | 上海泽生科技开发有限公司 | 纽兰格林持续给药能改善心脏功能 |
| BRPI0620819A2 (pt) | 2005-12-30 | 2011-11-22 | Zensun Shangai Science & Technology Ltd | uso de uma neuregulina (nrg) de liberação prolongada, nrg em uma liberação prolongada de uma dosagem baixa constante, e, composição de liberação prolongada para prevenir, tratar ou retardar uma doença ou distúrbio em um mamìfero |
| US9580515B2 (en) | 2006-08-21 | 2017-02-28 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Neukinase, a downstream protein of neuregulin |
| CN101636656A (zh) | 2007-01-25 | 2010-01-27 | 霍夫曼-拉罗奇有限公司 | Igfbp-7在心力衰竭评估中的用途 |
| CN101310766B (zh) * | 2007-05-25 | 2014-04-16 | 上海泽生科技开发有限公司 | 神经调节蛋白的新用途 |
| CN101310779A (zh) | 2007-05-25 | 2008-11-26 | 上海泽生科技开发有限公司 | 包含神经调节蛋白的装置及药物制剂 |
| US20090156488A1 (en) | 2007-09-12 | 2009-06-18 | Zensun (Shanghai) Science & Technology Limited | Use of neuregulin for organ preservation |
| DK2320933T3 (en) * | 2008-07-17 | 2018-04-16 | Acorda Therapeutics Inc | THERAPEUTIC DOSAGE OF A NEUREGULIN OR A SUBSEQUENT THEREOF FOR TREATMENT OR PROPHYLAXY OF HEART FAILURE |
| EP2808339B1 (en) | 2008-11-28 | 2017-02-15 | Zensun (Shanghai) Science & Technology, Co., Ltd. | Neuregulin peptides and their use |
| WO2010060266A1 (en) | 2008-11-28 | 2010-06-03 | Zensun (Shanghai) Science & Technology Limited | Neuregulin and cardiac stem cells |
| WO2010142141A1 (en) | 2009-06-09 | 2010-12-16 | Zensun (Shanghai) Science & Technology Limited | Neuregulin based methods for treating heart failure |
| CN102470161A (zh) | 2009-06-09 | 2012-05-23 | 上海泽生科技开发有限公司 | 神经调节蛋白用于治疗心力衰竭的有效剂量 |
| JP6096262B2 (ja) | 2009-08-25 | 2017-03-15 | ゼンサン （シャンハイ） サイエンス アンド テクノロジー，シーオー．，エルティーディー． | ニューレグリンに基づく心不全の治療方法 |
| CN102139095A (zh) | 2010-01-29 | 2011-08-03 | 上海泽生科技开发有限公司 | 神经调节蛋白用于预防、治疗或延迟心脏缺血再灌注损伤的方法和组合物 |
| JP5890785B2 (ja) | 2010-03-10 | 2016-03-22 | センプラ ファーマシューティカルズ，インコーポレイテッド | マクロライド抗生物質の非経口製剤 |
| EP2555788B1 (en) * | 2010-03-24 | 2017-10-11 | Massachusetts Institute of Technology | NEUREGULIN DIMER FOR AN ErbB/HER RECEPTOR FOR USE IN REDUCING CARDIOTOXICITY. |
| BR112013001594A2 (pt) | 2010-07-22 | 2016-05-17 | Reven Pharmaceuticals Inc | métodos de tratamento ou melhoria de doenças e para melhorar o desempenho compreendendo o uso de uma solução dipolo magnético estabilizada |
| WO2013053076A1 (en) | 2011-10-10 | 2013-04-18 | Zensun （Shanghai）Science & Technology Limited | Compositions and methods for treating heart failure |
| AU2013243955B2 (en) | 2012-04-02 | 2018-02-22 | Modernatx, Inc. | Modified polynucleotides for the production of oncology-related proteins and peptides |
| JP6475623B2 (ja) | 2012-10-08 | 2019-02-27 | ゼンスン（シャンハイ）サイエンス アンド テクノロジー カンパニー リミテッド | 糖尿病患者における心不全の治療用組成物 |
| CA2904055A1 (en) * | 2013-03-06 | 2014-09-12 | Acorda Therapeutics, Inc. | Therapeutic dosing of a neuregulin or a fragment thereof for treatment or prophylaxis of heart failure |
| CA2911848A1 (en) | 2013-05-22 | 2014-11-27 | Zensun (Shanghai) Science & Technology, Ltd. | Extended release of neuregulin for treating heart failure |
| CN104758300A (zh) | 2014-01-02 | 2015-07-08 | 上海泽生科技开发有限公司 | 维生素d及其组合物的抗菌用途 |
| CN110946993A (zh) | 2014-01-03 | 2020-04-03 | 上海泽生科技开发股份有限公司 | 纽兰格林制剂的配方 |
| CN105497876B (zh) | 2014-09-24 | 2021-01-15 | 上海泽生科技开发股份有限公司 | 神经调节蛋白用于预防、治疗或延迟心脏室性心律失常的方法和组合物 |
-
2014
- 2014-10-17 CN CN201410550212.7A patent/CN105561298A/zh active Pending
- 2014-10-17 CN CN202010283482.1A patent/CN111407882A/zh active Pending
-
2015
- 2015-10-08 WO PCT/CN2015/091459 patent/WO2016058493A1/zh not_active Ceased
- 2015-10-08 CN CN201580054201.2A patent/CN108064164A/zh active Pending
- 2015-10-08 EP EP15850529.7A patent/EP3207940B1/en active Active
- 2015-10-08 AU AU2015333335A patent/AU2015333335B2/en active Active
- 2015-10-08 EP EP22174662.1A patent/EP4112068A1/en active Pending
- 2015-10-08 US US15/518,730 patent/US10561709B2/en active Active
- 2015-10-08 ES ES15850529T patent/ES2924395T3/es active Active
- 2015-10-08 JP JP2017520447A patent/JP2017532343A/ja active Pending
- 2015-10-08 CA CA2963322A patent/CA2963322A1/en not_active Abandoned
- 2015-10-08 KR KR1020177010326A patent/KR102603711B1/ko active Active
- 2015-10-08 RU RU2017116973A patent/RU2017116973A/ru not_active Application Discontinuation
- 2015-10-08 KR KR1020237039263A patent/KR20230159650A/ko not_active Ceased
-
2019
- 2019-12-13 US US16/714,397 patent/US20200368317A1/en not_active Abandoned
-
2020
- 2020-08-21 JP JP2020139931A patent/JP2020193217A/ja active Pending
-
2021
- 2021-10-29 AU AU2021258063A patent/AU2021258063B2/en active Active
- 2021-12-21 US US17/558,451 patent/US20220354928A1/en not_active Abandoned
-
2022
- 2022-07-06 JP JP2022108771A patent/JP2022153417A/ja active Pending
-
2024
- 2024-08-14 JP JP2024135192A patent/JP2024164068A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111407881A (zh) * | 2019-01-07 | 2020-07-14 | 上海泽生科技开发股份有限公司 | 神经调节蛋白用于预防、治疗或延迟心肌损伤的方法和组合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108064164A (zh) | 2018-05-22 |
| US20200368317A1 (en) | 2020-11-26 |
| CN105561298A (zh) | 2016-05-11 |
| US20220354928A1 (en) | 2022-11-10 |
| AU2015333335B2 (en) | 2021-08-05 |
| JP2022153417A (ja) | 2022-10-12 |
| EP4112068A1 (en) | 2023-01-04 |
| KR20230159650A (ko) | 2023-11-21 |
| JP2020193217A (ja) | 2020-12-03 |
| RU2017116973A3 (enExample) | 2019-05-06 |
| CN111407882A (zh) | 2020-07-14 |
| US20170232068A1 (en) | 2017-08-17 |
| ES2924395T3 (es) | 2022-10-06 |
| EP3207940B1 (en) | 2022-06-01 |
| US10561709B2 (en) | 2020-02-18 |
| KR20170066440A (ko) | 2017-06-14 |
| EP3207940A1 (en) | 2017-08-23 |
| WO2016058493A1 (zh) | 2016-04-21 |
| AU2015333335A1 (en) | 2017-04-20 |
| JP2017532343A (ja) | 2017-11-02 |
| KR102603711B1 (ko) | 2023-11-20 |
| JP2024164068A (ja) | 2024-11-26 |
| EP3207940A4 (en) | 2018-06-06 |
| AU2021258063A1 (en) | 2021-11-25 |
| RU2017116973A (ru) | 2018-11-19 |
| AU2021258063B2 (en) | 2025-02-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2021258063B2 (en) | Methods and compositions of neuregulins for preventing, treating or delaying preserved ejection fraction cardiac failure | |
| JP7761964B2 (ja) | 心不全の治療用組成物 | |
| US12208158B2 (en) | Extended release of neuregulin for treating heart failure | |
| EP3199174B1 (en) | Uses of neuregulin in preventing, treating or delaying ventricular arrhythmia | |
| CN102159236A (zh) | 用于治疗或预防心力衰竭的神经调节蛋白或其亚序列的治疗性施剂 | |
| CN117866072A (zh) | 神经调节蛋白多肽片段及其用途 | |
| HK1241737B (en) | Compositions of a neuregulin for preventing, treating or delaying preserved ejection fraction cardiac failure | |
| HK1241737A1 (en) | Compositions of a neuregulin for preventing, treating or delaying preserved ejection fraction cardiac failure | |
| JP2022516199A (ja) | ニューレグリンを用いて心筋損傷を予防、治療、又は緩和するための方法及びそのための組成物 | |
| CN120018856A (zh) | 神经调节蛋白及其应用 | |
| HK1241715B (zh) | 用於治疗或预防心力衰竭的神经调节蛋白或其亚序列的治疗性施剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20211229 |
|
| FZDE | Discontinued |
Effective date: 20211229 |
|
| FZDE | Discontinued |
Effective date: 20211229 |