DK2379067T3 - Doseringsregimen for fingolimod til behandling af multipel sklerose - Google Patents
Doseringsregimen for fingolimod til behandling af multipel sklerose Download PDFInfo
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- DK2379067T3 DK2379067T3 DK09797234.3T DK09797234T DK2379067T3 DK 2379067 T3 DK2379067 T3 DK 2379067T3 DK 09797234 T DK09797234 T DK 09797234T DK 2379067 T3 DK2379067 T3 DK 2379067T3
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- 238000011282 treatment Methods 0.000 title claims description 98
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 title claims description 42
- 201000006417 multiple sclerosis Diseases 0.000 title claims description 26
- 229960000556 fingolimod Drugs 0.000 title description 37
- 239000003814 drug Substances 0.000 claims description 47
- 229940079593 drug Drugs 0.000 claims description 46
- 150000003839 salts Chemical group 0.000 claims description 44
- 150000001875 compounds Chemical class 0.000 claims description 29
- 230000000694 effects Effects 0.000 claims description 20
- 238000002560 therapeutic procedure Methods 0.000 claims description 12
- 230000001225 therapeutic effect Effects 0.000 claims description 11
- 230000000747 cardiac effect Effects 0.000 claims description 7
- 238000011283 initial treatment period Methods 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 206010033557 Palpitations Diseases 0.000 claims description 4
- 208000002173 dizziness Diseases 0.000 claims description 4
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 claims description 3
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- 229910019142 PO4 Inorganic materials 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 2
- 239000010452 phosphate Substances 0.000 claims 2
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 claims 1
- 239000000556 agonist Substances 0.000 description 89
- 229940044601 receptor agonist Drugs 0.000 description 87
- 229940075993 receptor modulator Drugs 0.000 description 85
- 229940126062 Compound A Drugs 0.000 description 39
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 39
- 229940002612 prodrug Drugs 0.000 description 33
- 239000000651 prodrug Substances 0.000 description 33
- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 description 31
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 239000000018 receptor agonist Substances 0.000 description 9
- 239000003416 antiarrhythmic agent Substances 0.000 description 8
- 206010003671 Atrioventricular Block Diseases 0.000 description 7
- 238000011287 therapeutic dose Methods 0.000 description 7
- 238000004448 titration Methods 0.000 description 7
- 206010003119 arrhythmia Diseases 0.000 description 6
- 238000012544 monitoring process Methods 0.000 description 6
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 6
- 206010003677 Atrioventricular block second degree Diseases 0.000 description 5
- 206010040639 Sick sinus syndrome Diseases 0.000 description 5
- 239000002876 beta blocker Substances 0.000 description 5
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- 230000000977 initiatory effect Effects 0.000 description 5
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- 241000282414 Homo sapiens Species 0.000 description 4
- 230000006793 arrhythmia Effects 0.000 description 4
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- LRFKWQGGENFBFO-UHFFFAOYSA-N fingolimod phosphate Chemical group CCCCCCCCC1=CC=C(CCC(N)(CO)COP(O)(O)=O)C=C1 LRFKWQGGENFBFO-UHFFFAOYSA-N 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000011269 treatment regimen Methods 0.000 description 4
- ITPDYQOUSLNIHG-UHFFFAOYSA-N Amiodarone hydrochloride Chemical compound [Cl-].CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCC[NH+](CC)CC)C(I)=C1 ITPDYQOUSLNIHG-UHFFFAOYSA-N 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 238000011292 agonist therapy Methods 0.000 description 3
- 229960005260 amiodarone Drugs 0.000 description 3
- 230000003288 anthiarrhythmic effect Effects 0.000 description 3
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 229960000244 procainamide Drugs 0.000 description 3
- REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 description 3
- 229960001404 quinidine Drugs 0.000 description 3
- 229960002370 sotalol Drugs 0.000 description 3
- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 3
- 206010042772 syncope Diseases 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
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- 208000006218 bradycardia Diseases 0.000 description 2
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- 210000001986 peyer's patch Anatomy 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 108010072051 Glatiramer Acetate Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010040738 Sinus arrest Diseases 0.000 description 1
- 102100025750 Sphingosine 1-phosphate receptor 1 Human genes 0.000 description 1
- 101710155454 Sphingosine 1-phosphate receptor 1 Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 235000021152 breakfast Nutrition 0.000 description 1
- 230000011128 cardiac conduction Effects 0.000 description 1
- 210000004970 cd4 cell Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- SWZTYAVBMYWFGS-UHFFFAOYSA-N fingolimod hydrochloride Chemical group Cl.CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 SWZTYAVBMYWFGS-UHFFFAOYSA-N 0.000 description 1
- -1 for example Proteins 0.000 description 1
- 229960003776 glatiramer acetate Drugs 0.000 description 1
- 102000034345 heterotrimeric G proteins Human genes 0.000 description 1
- 108091006093 heterotrimeric G proteins Proteins 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229960001388 interferon-beta Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001047 pyretic effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 201000002932 second-degree atrioventricular block Diseases 0.000 description 1
- DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Transplantation (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (11)
1. Forbindelse betegnet 2-amino-2-[2-(4-octylphenyl)ethyl]propan-1,3-diol i fri form eller i en farmaceutisk acceptabel saltform eller phosphatet deraf med formlen Ila,
hvor R2a er H, R3a er OH, Xa er O, R1a og R1b er OH, til anvendelse i behandlingen af multipel sklerose, hvor i den initiale behandlingsperiode forbindelsen gives ved en initial daglig dosering på 0,125 mg og efterfølgende ved en daglig dosering på 0,25 mg, og derefter fortsætter behandlingen med den daglige standarddosering på 0,5 mg.
2. Forbindelse ifølge krav 1 til anvendelse i behandlingen ifølge krav 1, hvor varigheden af den initiale behandlingsperiode er udvalgt fra gruppen bestående af: 4 til 12 dage, 5 til 14 dage, op til 10 dage, 7 til 10 dage, 9 dage, 8 dage, 7 dage, 6 dage, 5 dage eller 4 dage.
3. Forbindelse ifølge krav 1 til anvendelse i behandlingen ifølge krav 1, hvor varigheden af den initiale behandlingsperiode er 7 til 10 dage.
4. Forbindelse ifølge krav 1 til anvendelse i behandlingen ifølge et hvilket som helst af kravene 1 til 3 hos en patient med risiko for kardiale bivirkninger eller hjerteinsufficiens.
5. Forbindelse ifølge krav 1 til anvendelse i behandlingen ifølge et hvilket som helst af kravene 1 til 3, mens forekomsten af symptomer, indbefattende svimmelhed, træthed og hjertepalpitationer, begrænses, reduceres eller forebygges.
6. Forbindelse ifølge krav 1 til anvendelse i behandlingen ifølge et hvilket som helst af kravene 1 til 5, hvor forbindelsen administreres til patienter, der har haft en afbrydelse af eller terapeutisk behandlingspause med forbindelsen.
7. Forbindelse ifølge krav 1 til anvendelse i behandlingen ifølge et hvilket som helst af kravene 1 til 6, hvor multipel sklerose er recidiverende-remitterende multipel sklerose eller primær progressiv multipel sklerose.
8. Forbindelse ifølge krav 1 til anvendelse i behandlingen ifølge et hvilket som helst af kravene 1 til 7, hvor forbindelsen er 2-amino-2-[2-(4-octylphenyl)ethyl]propan-1,3-diol i fri form eller hydrochloridet deraf.
9. Kit omfattende medicineringsenheder af en forbindelse betegnet 2-amino-2-[2-(4-octylphenyl)ethyl]propan-1,3-diol i fri form eller i en farmaceutisk acceptabel saltform eller phosphatet deraf med formlen Ila
hvor R2a er H, R3a er OH, Xa er O, Ria og Rib er OH, til anvendelse i behandlingen ifølge krav 1, hvori medicineringsenhederne indeholder de daglige doseringer ifølge krav 1 til administration til patienten i den initiale behandlingsperiode.
10. Kit ifølge krav 9 til anvendelse i behandlingen ifølge krav 1, hvilket kit endvidere omfatter enheder til den daglige standarddosering på 0,5 mg af forbindelsen.
11. Kit ifølge krav 9 eller 10 til anvendelse i behandlingen ifølge krav 1, hvor forbindelsen er 2-amino-2-[2-(4-octylphenyl)ethyl]propan-1,3-diol i fri form eller hydrochloridet deraf.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13967208P | 2008-12-22 | 2008-12-22 | |
| US21853009P | 2009-06-19 | 2009-06-19 | |
| US24671509P | 2009-09-29 | 2009-09-29 | |
| PCT/US2009/068888 WO2010075239A1 (en) | 2008-12-22 | 2009-12-21 | Dosage regimen for a s1p receptor agonist |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2379067T3 true DK2379067T3 (da) | 2015-12-07 |
Family
ID=41667217
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK22187007.4T DK4098256T5 (da) | 2008-12-22 | 2009-12-21 | Doseringsregime for en s1p-receptoragonist |
| DK18179301.9T DK3409274T3 (da) | 2008-12-22 | 2009-12-21 | Doseringsskema for en s1p-receptoragonist |
| DK18201062.9T DK3453387T3 (da) | 2008-12-22 | 2009-12-21 | Doseringsplan til en s1p-receptoragonist |
| DK09797234.3T DK2379067T3 (da) | 2008-12-22 | 2009-12-21 | Doseringsregimen for fingolimod til behandling af multipel sklerose |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK22187007.4T DK4098256T5 (da) | 2008-12-22 | 2009-12-21 | Doseringsregime for en s1p-receptoragonist |
| DK18179301.9T DK3409274T3 (da) | 2008-12-22 | 2009-12-21 | Doseringsskema for en s1p-receptoragonist |
| DK18201062.9T DK3453387T3 (da) | 2008-12-22 | 2009-12-21 | Doseringsplan til en s1p-receptoragonist |
Country Status (43)
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2278960T5 (pl) | 2008-03-17 | 2020-06-29 | Actelion Pharmaceuticals Ltd. | Schemat dawkowania dla selektywnego agonisty receptora sip1 |
| TW201028143A (en) | 2008-12-22 | 2010-08-01 | Novartis Ag | Dosage regimen for a S1P receptor agonist |
| NZ598534A (en) | 2009-09-29 | 2014-03-28 | Novartis Ag | Dosage regimen of an s1p receptor modulator |
| US20110124605A1 (en) * | 2009-11-20 | 2011-05-26 | Shreeram Aradhye | Use of an S1P Receptor Agonist |
| JP5856980B2 (ja) | 2010-01-27 | 2016-02-10 | アリーナ ファーマシューティカルズ， インコーポレイテッド | （Ｒ）−２−（７−（４−シクロペンチル−３−（トリフルオロメチル）ベンジルオキシ）−１，２，３，４−テトラヒドロシクロペンタ［ｂ］インドール−３−イル）酢酸およびその塩の調製のためのプロセス |
| BR112012028248A2 (pt) * | 2010-05-06 | 2016-08-02 | Novartis Ag | derivados de sulfeto de diarila, seu uso, e kit |
| EP2455080A1 (en) * | 2010-11-23 | 2012-05-23 | Almirall, S.A. | S1P1 receptor agonists for use in the treatment of multiple sclerosis |
| FR2968556B1 (fr) | 2010-12-13 | 2013-12-27 | Centre Nat Rech Scient | Inhibiteurs des infections a vih et leurs utilisations |
| JP6111202B2 (ja) | 2011-01-07 | 2017-04-05 | ノバルティス アーゲー | 免疫抑制製剤 |
| EP3502236B1 (en) | 2011-02-18 | 2023-08-23 | The Scripps Research Institute | Directed differentiation of oligodendrocyte precursor cells to a myelinating cell fate |
| AR085749A1 (es) | 2011-04-01 | 2013-10-23 | Novartis Ag | Formulaciones |
| US9592268B2 (en) | 2011-05-23 | 2017-03-14 | Cornell University | Endothelium protective materials and methods of use |
| TW201320994A (zh) * | 2011-10-11 | 2013-06-01 | Novartis Ag | 投藥療程 |
| SMT202000298T1 (it) | 2012-08-17 | 2020-07-08 | Actelion Pharmaceuticals Ltd | Processo per la produzione di (2z,5z)-5-(3-cloro-4((r)-2,3-diidrossipropossi) benziliden)-2-(propilimmino)-3-(o-tolil)tiazolidin-4-one e intermedio usato in detto processo |
| JP6542678B2 (ja) * | 2013-03-06 | 2019-07-10 | アコーダ セラピューティクス インコーポレイテッド | 心不全の治療または予防のためのニューレグリンまたはその断片の治療的投与の方法 |
| US10675254B2 (en) | 2013-10-11 | 2020-06-09 | Teikoku Seiyaku Co., Ltd. | Sphingosine-1-phosphate receptor agonist iontophoretic devices and methods of using the same |
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