SI3023506T1 - Postopek zdravljenja na osnovi polimorfizmov gena KCNQ1 - Google Patents
Postopek zdravljenja na osnovi polimorfizmov gena KCNQ1 Download PDFInfo
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- SI3023506T1 SI3023506T1 SI201031707T SI201031707T SI3023506T1 SI 3023506 T1 SI3023506 T1 SI 3023506T1 SI 201031707 T SI201031707 T SI 201031707T SI 201031707 T SI201031707 T SI 201031707T SI 3023506 T1 SI3023506 T1 SI 3023506T1
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- 238000000034 method Methods 0.000 title claims abstract 15
- 102000054765 polymorphisms of proteins Human genes 0.000 title claims 2
- 108090000623 proteins and genes Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 17
- 108010011185 KCNQ1 Potassium Channel Proteins 0.000 claims 10
- 102000014021 KCNQ1 Potassium Channel Human genes 0.000 claims 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 7
- 208000035475 disorder Diseases 0.000 claims 7
- 108010001237 Cytochrome P-450 CYP2D6 Proteins 0.000 claims 6
- 102100021704 Cytochrome P450 2D6 Human genes 0.000 claims 6
- 208000028017 Psychotic disease Diseases 0.000 claims 6
- XMXHEBAFVSFQEX-UHFFFAOYSA-N iloperidone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 XMXHEBAFVSFQEX-UHFFFAOYSA-N 0.000 claims 3
- 229960003162 iloperidone Drugs 0.000 claims 3
- SBKZGLWZGZQVHA-UHFFFAOYSA-N 1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-methoxyphenyl]ethanol Chemical compound COC1=CC(C(C)O)=CC=C1OCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 SBKZGLWZGZQVHA-UHFFFAOYSA-N 0.000 claims 2
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims 2
- 206010026749 Mania Diseases 0.000 claims 2
- 208000020186 Schizophreniform disease Diseases 0.000 claims 2
- 208000000323 Tourette Syndrome Diseases 0.000 claims 2
- 208000016620 Tourette disease Diseases 0.000 claims 2
- 208000022610 schizoaffective disease Diseases 0.000 claims 2
- 201000000980 schizophrenia Diseases 0.000 claims 2
- 206010047571 Visual impairment Diseases 0.000 claims 1
- 208000029257 vision disease Diseases 0.000 claims 1
- 230000004393 visual impairment Effects 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- 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
- A61P9/06—Antiarrhythmics
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- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
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- C12Q2600/00—Oligonucleotides characterized by their use
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- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
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- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
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- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (13)
- Postopek zdravljenja na osnovi polimorfizmov gena KCNQ1 Patentni zahtevki1. Spojina, ki vsebuje iloperidon ali 1-|4-[3-[4-(6-fluoro-l,2-benzisoksazol-3-il)-l-piperidinil]propoksi]-3-metoksifenil]etanol za uporabo v zdravljenju motnje v posamezniku, pri katerem je ugotovljeno, daje njegov genotip KCNQ1 povezan s povečanim tveganjem za podaljšanje intervala QT, kjer je količina spojine, ki bo administrirana posamezniku manj kot 24 mg/dan in manj, kot bi jo bilo administrirane posamezniku, ki ima genotip KCNQ1, ki ni povezan s povečanim tveganjem za podaljšanje intervala QT. kjer je motnja shizofrenija, shizoafektivna motnja, depresija, bipolarna manična/depresija, Touretteov sindrom, psihotična motnja, motnja prividov ali shizofreniformna motnja in, kjer je genotip KCNQ1 povezan s povečanim tveganjem za podaljšanje intervala QT AA na položaju 286414 referenčnega zaporedja AJ006345.1 ali TT na položaju 2483474 referenčnega zaporedja AJ006345.1.
- 2. Spojina za uporabo v zdravljenju motnje po zahtevku 1, kjer je tudi posameznikov genotip CYP2D6 povezan s povečanim tveganjem za podaljšanje intervala QT.
- 3. Spojina za uporabo v zdravljenju motnje po zahtevku 2, kjer je količina administrirane spojine manjša, če je posameznikov genotip CYP2D6G1846A AA ali GA, kot če je posameznikov genotip CYP2D6G1846A GG.
- 4. Spojina za uporabo v zdravljenju motnje po zahtevku 2, kjer je količina administrirane spojine manjša, če je posameznikov genotip CYP2D6C100T TT ali CT, kot če je posameznikov genotip CYP2D6C100T CC.
- 5. Postopek določanja odmerka spojine, ki je iloperidon ali l-[4-[3-[4-(6-fluoro-l,2-benzisoksazol-3-il)-l-piperidinil]propoksi]-3-metoksifenil]etanol, za administracijo posamezniku, ki trpi za motnjo, kjer je motnja shizofrenija, shizoafektivna motnja, depresija, bipolarna manična/depresija, Touretteov sindrom, psihotična motnja, motnja prividov ali shizofreniformna motnja, kjer omenjeni postopek obsega: ugotavljanje, ali je posameznikov genotip KCNQ1 povezan s povečanim tveganjem za podaljšanje intervala QT, kjer je genotip KCNQ1 povezan s povečanim tveganjem za podaljšanje intervala QT, če je genotip KCNQ1 AA na položaju 286414 referenčnega zaporedja AJ006345.1 ali TT na položaju 2483474 referenčnega zaporedja AJ006345.1 in, če je posameznikov genotip KCNQ1 povezan s povečanim tveganjem za podaljšanje intervala QT, nato določanje, daje odmerek spojine za administracijo posamezniku manj kot 24 mg/dan in je manjši, kot bi bila administrirana posamezniku, če bi imel genotip KCNQ1, ki ni povezan s povečanim tveganjem za podaljšanje intervala QT.
- 6. Postopek po zahtevku 5, ki nadalje obsega: ugotavljanje, ali je posameznikov genotip CYP2D6 povezan s povečanim tveganjem za podaljšanje intervala QT in, če je posameznikov genotip CYP2D6 povezan s povečanim tveganjem za podaljšanje intervala QT. nato določanje, daje odmerek spojine za administracijo posamezniku manj kot 24 mg/dan je manjši, kot bi bila administrirana posamezniku, če bi imel genotip CYP2D6, ki ni povezan s povečanim tveganjem za podaljšanje intervala QT.
- 7. Postopek po zahtevku 6, kjer je količina spojine za administracijo posamezniku manjša, če je posameznikov genotip CYP2D6G1846A AA ali GA, kot če je posameznikov genotip CYP2D6G1846A GG.
- 8. Postopek po zahtevku 6. kjer je količina spojine za administracijo posamezniku manjša, če je posameznikov genotip CYP2D6C100T TT ali CT, kot če je posameznikov genotip CYP2D6C100T CC.
- 9. Postopek ugotavljanja ali je posameznik izpostavljen tveganju za podaljšanje intervala QT, kjer omenjeni postopek obsega: ugotavljanje posameznikovega genotip KCNQ1 na položaju 286414 ali 2483474 referenčnega zaporedja AJ006345.1 in, če je posamenikov genotip na položaju 286414 AA ali je posamenikov genotip na položaju 2483474 TT, nato določanje, da je posameznik izpostavljen povečanemu tveganju za podaljšanje intervala QT.
- 10. Postopek po zahtevku 9. ki nadalje obsega ugotavljanje posameznikovega genotipa CYP2D6 in, če je posameznikov genotip CYP2D6G1846A AA ali GA, določanje, da je posameznik izpostavljen večjemu tveganju za podaljšanje intervala QT, kot če je posameznikov genotip CYP2D6G1846A GG.
- 11. Postopek po zahtevku 9, i nadalje obsega ugotavljanje posameznikovega genotipa CYP2D6 in. če je posameznikov genotip CYP2D6C100T TT ali CT, določanje, daje posameznik izpostavljen večjemu tveganju za podaljšanje intervala QT, kot če je posameznikov genotip CYP2D6C100T CC.
- 12. Spojina po kateremkoli zahtevku od 1 do 4 ali postopek po kateremkoli zahtevku od 5 do 11, kjer je spojina iloperidon.
- 13. Spojina po kateremkoli zahtevku od 1 do 4 ali postopek po kateremkoli zahtevku od 5 do 11, kjer je spojina l-|4-[3-[4-(6-fluoro-l,2-benzisoksazol-3-il)-l-piperidinil]propoksi]-3-metoksifeniljetanol.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16713609P | 2009-04-06 | 2009-04-06 | |
| EP15199673.3A EP3023506B1 (en) | 2009-04-06 | 2010-04-05 | Method of treatment based on polymorphisms of the kcnq1 gene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI3023506T1 true SI3023506T1 (sl) | 2018-08-31 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI201031707T SI3023506T1 (sl) | 2009-04-06 | 2010-04-05 | Postopek zdravljenja na osnovi polimorfizmov gena KCNQ1 |
| SI201031328T SI2417267T1 (sl) | 2009-04-06 | 2010-04-05 | Postopek zdravljenja na podlagi polimorfizmov gena KCNQ1 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI201031328T SI2417267T1 (sl) | 2009-04-06 | 2010-04-05 | Postopek zdravljenja na podlagi polimorfizmov gena KCNQ1 |
Country Status (8)
| Country | Link |
|---|---|
| US (4) | US8999638B2 (sl) |
| EP (3) | EP2417267B1 (sl) |
| JP (2) | JP5800798B2 (sl) |
| CA (1) | CA2757713C (sl) |
| ES (3) | ES2792126T3 (sl) |
| HU (2) | HUE030667T2 (sl) |
| SI (2) | SI3023506T1 (sl) |
| WO (1) | WO2010117931A1 (sl) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108938632A (zh) | 2012-03-14 | 2018-12-07 | 万达制药公司 | 用于治疗精神疾病的伊潘立酮代谢物及其应用 |
| JP2019532011A (ja) * | 2016-11-02 | 2019-11-07 | アログ・ファーマシューティカルズ・インコーポレイテッドＡｒｏｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | Ｆｌｔ３突然変異増殖性疾患および関連する突然変異を治療するためのクレノラニブ |
| JP7199361B2 (ja) * | 2017-01-27 | 2023-01-05 | ニューロクライン バイオサイエンシーズ，インコーポレイテッド | 特定のｖｍａｔ２インヒビターを投与するための方法 |
| IL309802A (en) | 2017-09-21 | 2024-02-01 | Neurocrine Biosciences Inc | High dose valbenazine formulation and related preparations, methods and kits |
| CN111836543A (zh) | 2017-10-10 | 2020-10-27 | 纽罗克里生物科学有限公司 | 施用某些vmat2抑制剂的方法 |
| CN109371125A (zh) * | 2018-12-31 | 2019-02-22 | 山西医科大学 | 基于kcnq1的心源性猝死相关snp检测试剂盒及检测方法 |
| US11607408B2 (en) | 2019-10-15 | 2023-03-21 | Vanda Pharmaceuticals Inc. | Method of treatment of schizophrenia |
| WO2023201182A1 (en) | 2022-04-13 | 2023-10-19 | Vanda Pharmaceuticals Inc. | Treatment of parkinson's disease and parkinson's disease psychosis |
| NL2033031B1 (en) * | 2022-08-22 | 2024-03-04 | Jiangsu Vocational College Medicine | Single nucleotide polymorphism (snp) molecular marker and kit for assessing tumor progression risk of patient with carcinoma of colon and rectum, and use thereof |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6345A (en) * | 1849-04-17 | Coefee-eoaster | ||
| US5364866A (en) | 1989-05-19 | 1994-11-15 | Hoechst-Roussel Pharmaceuticals, Inc. | Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analetics |
| US5776963A (en) | 1989-05-19 | 1998-07-07 | Hoechst Marion Roussel, Inc. | 3-(heteroaryl)-1- (2,3-dihydro-1h-isoindol-2-yl)alkyl!pyrrolidines and 3-(heteroaryl)-1- (2,3-dihydro-1h-indol-1-yl)alkyl!pyrrolidines and related compounds and their therapeutic untility |
| WO1993009276A1 (en) | 1991-11-01 | 1993-05-13 | National-Standard Company | Age resistant solder coatings |
| AU779477B2 (en) | 1999-08-09 | 2005-01-27 | University Of Utah Research Foundation | Alterations in the long QT syndrome genes KVLQT1 and SCN5A and methods for detecting same |
| DE60131970T2 (de) * | 2000-04-13 | 2008-12-11 | Georgetown University | Genetische diagnose zur feststellung von qt-verlängerungen als unerwünschte reaktion auf arzneimittel |
| EP1425415A2 (en) | 2001-08-20 | 2004-06-09 | Genaissance Pharmaceuticals, Inc. | Polymorphisms associated with ion-channel disease |
| US20050020632A1 (en) | 2001-08-31 | 2005-01-27 | Dominique Grimler | Optical isomers of an iloperidone metabolite |
| MXPA04006861A (es) * | 2002-01-18 | 2005-06-20 | Univ Utah Res Found | Deteccion de polimorfismos de nucleotidos individuales utilizando guias de onda planas. |
| AU2003286340A1 (en) | 2002-12-21 | 2004-07-14 | Pfizer Products Inc. | Methods and compositions relating to drug-induced arrhythmia |
| WO2006124646A2 (en) | 2005-05-13 | 2006-11-23 | University Of Chicago | Methods and compostions relating to the pharmacogenetics of different gene variants in the context of irinotecan-based therapies |
| WO2006009663A1 (en) * | 2004-06-22 | 2006-01-26 | Digimarc Corporation | Digital asset management, targeted searching and desktop searching using digital watermarks |
| US20060073506A1 (en) | 2004-09-17 | 2006-04-06 | Affymetrix, Inc. | Methods for identifying biological samples |
| CA3113166A1 (en) | 2004-09-30 | 2006-04-13 | Vanda Pharmaceuticals Inc. | Methods for the administration of iloperidone |
| ITMI20051047A1 (it) * | 2005-06-07 | 2006-12-08 | Irccs Fond Salvatore Maugeri C | Mutazioni associate alla sindrome del qt lungo e loro uso diagnostico |
| US20110077539A1 (en) | 2009-09-30 | 2011-03-31 | George Alfred L | Methods and Compositions for Prediction of Risk for Sudden Death in Long QT Syndrome |
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2010
- 2010-04-05 EP EP10713287.0A patent/EP2417267B1/en active Active
- 2010-04-05 SI SI201031707T patent/SI3023506T1/sl unknown
- 2010-04-05 CA CA2757713A patent/CA2757713C/en active Active
- 2010-04-05 EP EP15199673.3A patent/EP3023506B1/en active Active
- 2010-04-05 JP JP2012504743A patent/JP5800798B2/ja active Active
- 2010-04-05 ES ES18160989T patent/ES2792126T3/es active Active
- 2010-04-05 SI SI201031328T patent/SI2417267T1/sl unknown
- 2010-04-05 ES ES10713287.0T patent/ES2604102T3/es active Active
- 2010-04-05 EP EP18160989.2A patent/EP3354753B1/en active Active
- 2010-04-05 ES ES15199673.3T patent/ES2673603T3/es active Active
- 2010-04-05 HU HUE10713287A patent/HUE030667T2/en unknown
- 2010-04-05 US US13/263,074 patent/US8999638B2/en active Active
- 2010-04-05 HU HUE15199673A patent/HUE037724T2/hu unknown
- 2010-04-05 WO PCT/US2010/029921 patent/WO2010117931A1/en active Application Filing
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2015
- 2015-02-26 US US14/632,914 patent/US9157121B2/en active Active
- 2015-04-30 JP JP2015093382A patent/JP6108633B2/ja active Active
- 2015-09-01 US US14/841,884 patent/US20150368718A1/en not_active Abandoned
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2017
- 2017-09-14 US US15/705,048 patent/US10563259B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| ES2792126T3 (es) | 2020-11-10 |
| US20150368718A1 (en) | 2015-12-24 |
| EP2417267A1 (en) | 2012-02-15 |
| WO2010117931A1 (en) | 2010-10-14 |
| CA2757713A1 (en) | 2010-10-14 |
| SI2417267T1 (sl) | 2017-02-28 |
| US10563259B2 (en) | 2020-02-18 |
| US8999638B2 (en) | 2015-04-07 |
| JP2015180639A (ja) | 2015-10-15 |
| JP5800798B2 (ja) | 2015-10-28 |
| US20180002756A1 (en) | 2018-01-04 |
| EP3023506B1 (en) | 2018-03-14 |
| HUE037724T2 (hu) | 2018-09-28 |
| JP2012522838A (ja) | 2012-09-27 |
| EP3354753B1 (en) | 2020-02-12 |
| US20150167091A1 (en) | 2015-06-18 |
| US20120027871A1 (en) | 2012-02-02 |
| US9157121B2 (en) | 2015-10-13 |
| CA2757713C (en) | 2019-01-29 |
| EP3354753A1 (en) | 2018-08-01 |
| HUE030667T2 (en) | 2017-05-29 |
| EP3023506A1 (en) | 2016-05-25 |
| EP2417267B1 (en) | 2016-08-17 |
| ES2604102T3 (es) | 2017-03-03 |
| JP6108633B2 (ja) | 2017-04-05 |
| ES2673603T3 (es) | 2018-06-25 |
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