JP2004536077A5 - - Google Patents
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- JP2004536077A5 JP2004536077A5 JP2003501483A JP2003501483A JP2004536077A5 JP 2004536077 A5 JP2004536077 A5 JP 2004536077A5 JP 2003501483 A JP2003501483 A JP 2003501483A JP 2003501483 A JP2003501483 A JP 2003501483A JP 2004536077 A5 JP2004536077 A5 JP 2004536077A5
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- Japan
- Prior art keywords
- composition according
- polypeptide
- sequence
- sequence seq
- similarity
- 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.)
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- 229920001184 polypeptide Polymers 0.000 claims description 5
- 206010022979 Iron excess Diseases 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 3
- 150000007523 nucleic acids Chemical class 0.000 claims description 2
- 108020004707 nucleic acids Proteins 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 4
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims 3
- 206010018872 Haemochromatosis Diseases 0.000 claims 2
- 235000001014 amino acid Nutrition 0.000 claims 2
- 239000000969 carrier Substances 0.000 claims 2
- 230000005714 functional activity Effects 0.000 claims 2
- 102000018511 hepcidin family Human genes 0.000 claims 2
- 108060003558 hepcidin family Proteins 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 208000005846 Cardiomyopathy Diseases 0.000 claims 1
- 206010012601 Diabetes mellitus Diseases 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 201000008031 cardiomyopathy Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 238000002105 Southern blotting Methods 0.000 description 3
- 108010004073 cysteinylcysteine Proteins 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- OABOXRPGTFRBFZ-IMJSIDKUSA-N (2R)-2-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoic acid Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(O)=O OABOXRPGTFRBFZ-IMJSIDKUSA-N 0.000 description 1
- JSZMKEYEVLDPDO-ACZMJKKPSA-N (2R)-2-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-3-sulfanylpropanoic acid Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CS)C(O)=O JSZMKEYEVLDPDO-ACZMJKKPSA-N 0.000 description 1
- IJYZHIOOBGIINM-WDSKDSINSA-N Arg-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N IJYZHIOOBGIINM-WDSKDSINSA-N 0.000 description 1
- LVNMAAGSAUGNIC-UHFFFAOYSA-N Cysteinyl-Histidine Chemical compound SCC(N)C(=O)NC(C(O)=O)CC1=CN=CN1 LVNMAAGSAUGNIC-UHFFFAOYSA-N 0.000 description 1
- WXOFKRKAHJQKLT-UHFFFAOYSA-N Cysteinyl-Lysine Chemical compound NCCCCC(C(O)=O)NC(=O)C(N)CS WXOFKRKAHJQKLT-UHFFFAOYSA-N 0.000 description 1
- MFBYPDKTAJXHNI-VKHMYHEASA-N Gly-Cys Chemical compound [NH3+]CC(=O)N[C@@H](CS)C([O-])=O MFBYPDKTAJXHNI-VKHMYHEASA-N 0.000 description 1
- WMDZARSFSMZOQO-DRZSPHRISA-N Ile-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 WMDZARSFSMZOQO-DRZSPHRISA-N 0.000 description 1
- ZUKPVRWZDMRIEO-VKHMYHEASA-N L-cysteinylglycine zwitterion Chemical compound SC[C@H]([NH3+])C(=O)NCC([O-])=O ZUKPVRWZDMRIEO-VKHMYHEASA-N 0.000 description 1
- NDYNTQWSJLPEMK-UHFFFAOYSA-N Methionyl-Cysteine Chemical compound CSCCC(N)C(=O)NC(CS)C(O)=O NDYNTQWSJLPEMK-UHFFFAOYSA-N 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 108010016616 cysteinylglycine Proteins 0.000 description 1
- 229920003013 deoxyribonucleic acid Polymers 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 108010027338 isoleucylcysteine Proteins 0.000 description 1
Description
従って、本発明は、システイン残基を位置2、5、6、8、9、14、17および18に有し、次の配列:
Ile Cys Ile Phe Cys Cys Gly Cys Cys His Arg Ser Lys Cys Gly Met Cys Cys Lys Thr (SEQ ID NO: 1)
と少なくとも50%の同一性もしくは60%の類似性、好ましくは少なくとも60%の同一性もしくは少なくとも70%の類似性を有する20アミノ酸の配列を含むポリペプチドの使用、または鉄過剰を減少させるために有用である医薬品を製造するための、上記ポリペプチドをエンコードする核酸の使用を提案する。
Ile Cys Ile Phe Cys Cys Gly Cys Cys His Arg Ser Lys Cys Gly Met Cys Cys Lys Thr (SEQ ID NO: 1)
と少なくとも50%の同一性もしくは60%の類似性、好ましくは少なくとも60%の同一性もしくは少なくとも70%の類似性を有する20アミノ酸の配列を含むポリペプチドの使用、または鉄過剰を減少させるために有用である医薬品を製造するための、上記ポリペプチドをエンコードする核酸の使用を提案する。
サザンブロット
サザンブロットは、以前に記載されたように行った(VALLETら、J. Biol. Chem.、272、21944〜21949、1997)。HEPC1プローブを、次のプライマーとともに増幅した1437bpのマウスゲノムDNA断片から作成した:
−フォワード:
5'-GAGCAGCACCACCTATCTCCA-3'(SEQ ID NO:32)および
−リバース:
5'-AACAGATACCACAGGAGGGT-3'(SEQ ID NO:33)。
PvuIIで消化後、545bpの断片をアガロースゲルから精製してサザンブロットのプローブとして用いた。このHEPC1プローブは、相同のHEPC2領域と95%の同一性を示した。
サザンブロットは、以前に記載されたように行った(VALLETら、J. Biol. Chem.、272、21944〜21949、1997)。HEPC1プローブを、次のプライマーとともに増幅した1437bpのマウスゲノムDNA断片から作成した:
−フォワード:
5'-GAGCAGCACCACCTATCTCCA-3'(SEQ ID NO:32)および
−リバース:
5'-AACAGATACCACAGGAGGGT-3'(SEQ ID NO:33)。
PvuIIで消化後、545bpの断片をアガロースゲルから精製してサザンブロットのプローブとして用いた。このHEPC1プローブは、相同のHEPC2領域と95%の同一性を示した。
Claims (6)
- システイン残基を位置2、5、6、8、9、14、17および18に有し、配列SEQ ID NO:1と少なくとも70%の類似性を有し、かつ脊椎動物からのヘプシジンの成熟形態と同じ機能的活性を有する20アミノ酸の配列を含むポリペプチドと、適切な担体または賦形剤とを含む鉄過剰を減少させるための医薬組成物。
- システイン残基を位置2、5、6、8、9、14、17および18に有し、配列SEQ ID NO:1と少なくとも70%の類似性を有し、かつ脊椎動物からのヘプシジンの成熟形態と同じ機能的活性を有する20アミノ酸の配列を含むポリペプチドをコードする核酸と、適切な担体または賦形剤とを含む鉄過剰を減少させるための医薬組成物。
- 前記ポリペプチドが、配列SEQ ID NO:1を含む請求項1または2に記載の組成物。
- 脊椎動物が哺乳動物である、請求項1〜3のいずれか1つに記載の組成物。
- ヘモクロマトーシスの予防および/または治療に有用である、請求項1〜4のいずれか1つに記載の組成物。
- 肝癌、心筋症もしくは糖尿病から選択される、ヘモクロマトーシスに起因する疾患の予防および/または治療に有用である、請求項1〜4のいずれか1つに記載の組成物。
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP01401377.5 | 2001-05-25 | ||
EP01401377 | 2001-05-25 | ||
EP01401537A EP1262187A1 (en) | 2001-05-25 | 2001-06-14 | Use of hepcidin for preparing a medicament for treating disorders of iron homeostasis |
EP01401537.4 | 2001-06-14 | ||
EP02290795.0 | 2002-03-29 | ||
EP02290795 | 2002-03-29 | ||
PCT/EP2002/006924 WO2002098444A2 (en) | 2001-05-25 | 2002-05-24 | Use of hepcidin for preparing a medicament for treating disorders of iron homeostasis |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009006614A Division JP5717319B2 (ja) | 2001-05-25 | 2009-01-15 | 鉄ホメオスタシスの障害を治療するための医薬品を製造するためのヘプシジンの使用 |
JP2011263858A Division JP2012111755A (ja) | 2001-05-25 | 2011-12-01 | 鉄ホメオスタシスの調節剤としてのヘプシジンの使用 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2004536077A JP2004536077A (ja) | 2004-12-02 |
JP2004536077A5 true JP2004536077A5 (ja) | 2012-01-26 |
JP4944360B2 JP4944360B2 (ja) | 2012-05-30 |
Family
ID=27224392
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2003501483A Expired - Fee Related JP4944360B2 (ja) | 2001-05-25 | 2002-05-24 | 鉄ホメオスタシスの障害を治療するための医薬品を製造するためのヘプシジンの使用 |
JP2009006614A Expired - Lifetime JP5717319B2 (ja) | 2001-05-25 | 2009-01-15 | 鉄ホメオスタシスの障害を治療するための医薬品を製造するためのヘプシジンの使用 |
JP2011263858A Pending JP2012111755A (ja) | 2001-05-25 | 2011-12-01 | 鉄ホメオスタシスの調節剤としてのヘプシジンの使用 |
JP2014090333A Expired - Lifetime JP5847231B2 (ja) | 2001-05-25 | 2014-04-24 | 鉄ホメオスタシスの調節剤としてのヘプシジンの使用 |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009006614A Expired - Lifetime JP5717319B2 (ja) | 2001-05-25 | 2009-01-15 | 鉄ホメオスタシスの障害を治療するための医薬品を製造するためのヘプシジンの使用 |
JP2011263858A Pending JP2012111755A (ja) | 2001-05-25 | 2011-12-01 | 鉄ホメオスタシスの調節剤としてのヘプシジンの使用 |
JP2014090333A Expired - Lifetime JP5847231B2 (ja) | 2001-05-25 | 2014-04-24 | 鉄ホメオスタシスの調節剤としてのヘプシジンの使用 |
Country Status (12)
Country | Link |
---|---|
US (4) | US7169758B2 (ja) |
EP (2) | EP1392345B2 (ja) |
JP (4) | JP4944360B2 (ja) |
CN (2) | CN101884780B (ja) |
AT (1) | ATE427114T1 (ja) |
AU (1) | AU2002321105A1 (ja) |
CA (1) | CA2448382C (ja) |
CY (1) | CY1120241T1 (ja) |
DE (1) | DE60231804D1 (ja) |
ES (2) | ES2693050T3 (ja) |
TR (1) | TR201806761T4 (ja) |
WO (1) | WO2002098444A2 (ja) |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
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JP4944360B2 (ja) † | 2001-05-25 | 2012-05-30 | アンスティテュ ナシオナル ド ラ サント エ ド ラ ルシュルシェ メディカル(アンセルム) | 鉄ホメオスタシスの障害を治療するための医薬品を製造するためのヘプシジンの使用 |
US8017737B2 (en) | 2002-11-19 | 2011-09-13 | Hasan Kulaksiz | Diagnostic methods for diseases by screening for hepcidin in human or animal tissues, blood or body fluids; monoclonal antibodies specific to human hepcidin and associated uses therefor |
US7411048B2 (en) | 2002-11-19 | 2008-08-12 | Drg International, Inc. | Diagnostic method for diseases by screening for hepcidin in human or animal tissues, blood or body fluids |
EP1578254B1 (en) | 2002-11-19 | 2013-03-06 | DRG International, Inc. | Diagnostic method for diseases by screening for hepcidin in human or animal tissues, blood or body fluids and therapeutic uses therefor |
DE10349124A1 (de) | 2003-10-22 | 2005-05-19 | Roche Diagnostics Gmbh | Differenzialdiagnostik mit Hepcidin |
US20060063208A1 (en) | 2004-08-02 | 2006-03-23 | Woolf Clifford J | DRG11-responsive (DRAGON) gene and uses thereof |
KR100679100B1 (ko) * | 2004-10-29 | 2007-02-06 | 엘지.필립스 엘시디 주식회사 | 수평 전계 인가형 액정 표시 패널 및 그 제조방법 |
EP1858541B1 (en) * | 2005-02-16 | 2012-07-25 | The General Hospital Corporation | Use of bmp antagonists to regulate hepcidin-mediated iron metabolism and treat iron deficiency |
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AU2007275638B2 (en) * | 2006-07-21 | 2014-01-16 | Amgen Inc. | Method of detecting and/ or measuring hepcidin in a sample |
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US8895002B2 (en) | 2007-04-09 | 2014-11-25 | The General Hospital Corporation | Hemojuvelin fusion proteins and uses thereof |
WO2008146903A1 (ja) * | 2007-05-31 | 2008-12-04 | Naohisa Tomosugi | 活性型ヘプシジンを指標とした、急性虚血性疾患の診断方法 |
ES2385772T3 (es) | 2007-10-02 | 2012-07-31 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Anticuerpos específicos para la hepcidina humana |
WO2009055078A2 (en) | 2007-10-26 | 2009-04-30 | University Of Utah Research Foundation | Identification of the hepcidin binding site on ferroportin |
CL2008003190A1 (es) * | 2007-11-02 | 2009-09-04 | Lilly Co Eli | Anticuerpo que se enlaza selectivamente a hepcidina-25 humana madura; polinucleotido codificante, vector y celula huesped que lo comprende; uso medico para tratar la anemia, incrementar nivel de hierro, conteo de rediculocito, celulas rojas, hemoglobina, o hematocritos; proceso de produccion; composicion farmaceutica. |
WO2009139822A1 (en) | 2008-05-01 | 2009-11-19 | Amgen Inc. | Anti-hepcidin antibodies and methods of use |
CA2733497C (en) * | 2008-08-06 | 2015-06-02 | Eli Lilly And Company | Anti-hepcidin-25 selective antibodies and uses thereof |
US20100068737A1 (en) * | 2008-09-16 | 2010-03-18 | University Of Tennessee Research Foundation | Enzyme-linked Immunosorbent Assay (ELISA) for Canine Hepcidin |
CN102215869B (zh) | 2008-11-13 | 2015-05-13 | 通用医疗公司 | 用于通过调整bmp-6来调节铁稳态的方法和组合物 |
US8999935B2 (en) * | 2009-02-11 | 2015-04-07 | New York University | Treatment of osteoporosis in peri- and post-menopausal women with hepcidin |
DE102009034150A1 (de) * | 2009-07-20 | 2011-01-27 | Fresenius Medical Care Deutschland Gmbh | Adsorbens zur Adsorption von Hepcidin |
AR077892A1 (es) | 2009-08-20 | 2011-09-28 | Vifor Int Ag | Quinolinas antagonistas de la hepcidina |
AR077958A1 (es) | 2009-08-27 | 2011-10-05 | Vifor Int Ag | Quinoxalinonas antagonistas de la hepcidina |
AR077999A1 (es) | 2009-09-02 | 2011-10-05 | Vifor Int Ag | Antagonistas de pirimidin y triazin-hepcidina |
TW201113274A (en) | 2009-09-07 | 2011-04-16 | Vifor Int Ag | Novel ethanediamine hepcidine antagonists |
TW201111379A (en) | 2009-09-09 | 2011-04-01 | Vifor Int Ag | Novel thiazole-and oxazole-hepcidine-antagonists |
US20120214803A1 (en) | 2011-02-18 | 2012-08-23 | Vifor (International) Ag | Novel Sulfonaminoquinoline Hepcidin Antagonists |
EP2723861A4 (en) | 2011-06-21 | 2014-12-10 | Alnylam Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR INHIBITING HEPCIDINE ANTIMICROBIAL PEPTIDE (HAMP) OR THE ASSOCIATED GENE EXPRESSION |
CN103097531B (zh) * | 2011-06-29 | 2016-11-23 | 达纳福股份有限公司 | 生物样本的预处理方法、rna的检测方法及预处理试剂盒 |
US20140315817A1 (en) | 2011-11-18 | 2014-10-23 | Eleven Biotherapeutics, Inc. | Variant serum albumin with improved half-life and other properties |
ES2695166T3 (es) | 2013-03-15 | 2019-01-02 | Intrinsic Lifesciences Llc | Anticuerpos antihepcidina y usos de los mismos |
US20160051556A1 (en) | 2013-03-21 | 2016-02-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method and Pharmaceutical Composition for use in the Treatment of Chronic Liver Diseases Associated with a Low Hepcidin Expression |
WO2016049036A1 (en) | 2014-09-22 | 2016-03-31 | Intrinsic Lifesciences Llc | Humanized anti-hepcidin antibodies and uses thereof |
US10098878B2 (en) | 2014-10-10 | 2018-10-16 | The Board Of Regents Of The University Of Texas System | HIF-2α inhibitors for treating iron overload disorders |
MX2018008299A (es) * | 2016-01-08 | 2018-09-21 | La Jolla Pharma Co | Metodos para administrar hepcidina. |
WO2018165186A1 (en) * | 2017-03-07 | 2018-09-13 | Intrinsic Lifesciences Llc | Assessment of chronic iron deficiency |
WO2019165252A1 (en) * | 2018-02-23 | 2019-08-29 | La Jolla Pharmaceutical Company | Compositions comprising hepcidin and methods of use thereof |
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FR2766207B1 (fr) * | 1997-07-11 | 2000-12-08 | Rhone Poulenc Agrochimie | Gene chimere codant pour la drosomycine, vecteur le contenant pour la transformation des cellules vegetales et plantes transformees obtenues resistantes aux maladies |
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WO2000056879A1 (en) * | 1999-03-22 | 2000-09-28 | Universität Zürich | TRANSFORMING GROWTH FACTOR (TFG) β SUPERFAMILY ANTAGONISTS |
JP4944360B2 (ja) | 2001-05-25 | 2012-05-30 | アンスティテュ ナシオナル ド ラ サント エ ド ラ ルシュルシェ メディカル(アンセルム) | 鉄ホメオスタシスの障害を治療するための医薬品を製造するためのヘプシジンの使用 |
EP1578254B1 (en) † | 2002-11-19 | 2013-03-06 | DRG International, Inc. | Diagnostic method for diseases by screening for hepcidin in human or animal tissues, blood or body fluids and therapeutic uses therefor |
US7411048B2 (en) * | 2002-11-19 | 2008-08-12 | Drg International, Inc. | Diagnostic method for diseases by screening for hepcidin in human or animal tissues, blood or body fluids |
US8017737B2 (en) * | 2002-11-19 | 2011-09-13 | Hasan Kulaksiz | Diagnostic methods for diseases by screening for hepcidin in human or animal tissues, blood or body fluids; monoclonal antibodies specific to human hepcidin and associated uses therefor |
EP1858541B1 (en) * | 2005-02-16 | 2012-07-25 | The General Hospital Corporation | Use of bmp antagonists to regulate hepcidin-mediated iron metabolism and treat iron deficiency |
ES2427856T3 (es) * | 2006-09-16 | 2013-11-04 | Soy Labs Llc | Utilización de péptido de soja (lunasina) para reducir la tasa de colesterol total y LDL |
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ES2385772T3 (es) * | 2007-10-02 | 2012-07-31 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Anticuerpos específicos para la hepcidina humana |
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AU2009322260B2 (en) † | 2008-12-05 | 2013-09-12 | The Regents Of The University Of California | Mini-hepcidin peptides and methods of using thereof |
BR112014013697A2 (pt) | 2011-12-09 | 2020-11-03 | The Regents Of The University Of California | peptídeos mini-hepcidina modificados e métodos de uso dos mesmos |
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-
2002
- 2002-05-24 JP JP2003501483A patent/JP4944360B2/ja not_active Expired - Fee Related
- 2002-05-24 AU AU2002321105A patent/AU2002321105A1/en not_active Abandoned
- 2002-05-24 EP EP02754742.1A patent/EP1392345B2/en not_active Expired - Lifetime
- 2002-05-24 CA CA2448382A patent/CA2448382C/en not_active Expired - Lifetime
- 2002-05-24 TR TR2018/06761T patent/TR201806761T4/en unknown
- 2002-05-24 ES ES09004579.0T patent/ES2693050T3/es not_active Expired - Lifetime
- 2002-05-24 US US10/478,987 patent/US7169758B2/en not_active Expired - Lifetime
- 2002-05-24 CN CN201010232752.2A patent/CN101884780B/zh not_active Expired - Fee Related
- 2002-05-24 CN CN028148150A patent/CN1612746B/zh not_active Expired - Fee Related
- 2002-05-24 ES ES02754742.1T patent/ES2326469T5/es not_active Expired - Lifetime
- 2002-05-24 DE DE60231804T patent/DE60231804D1/de not_active Expired - Lifetime
- 2002-05-24 EP EP09004579.0A patent/EP2186524B1/en not_active Expired - Lifetime
- 2002-05-24 WO PCT/EP2002/006924 patent/WO2002098444A2/en active Application Filing
- 2002-05-24 AT AT02754742T patent/ATE427114T1/de not_active IP Right Cessation
-
2006
- 2006-11-21 US US11/602,402 patent/US9234903B2/en not_active Expired - Fee Related
-
2009
- 2009-01-15 JP JP2009006614A patent/JP5717319B2/ja not_active Expired - Lifetime
-
2011
- 2011-12-01 JP JP2011263858A patent/JP2012111755A/ja active Pending
-
2014
- 2014-04-24 JP JP2014090333A patent/JP5847231B2/ja not_active Expired - Lifetime
-
2015
- 2015-06-23 US US14/747,926 patent/US9782453B2/en not_active Expired - Lifetime
-
2017
- 2017-08-09 US US15/672,616 patent/US10004784B2/en not_active Expired - Lifetime
-
2018
- 2018-05-18 CY CY20181100516T patent/CY1120241T1/el unknown
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