DK1521831T3 - Transgent dyr der udtrykker trunkeret alzheimers tauprotein - Google Patents
Transgent dyr der udtrykker trunkeret alzheimers tauproteinInfo
- Publication number
- DK1521831T3 DK1521831T3 DK03763764T DK03763764T DK1521831T3 DK 1521831 T3 DK1521831 T3 DK 1521831T3 DK 03763764 T DK03763764 T DK 03763764T DK 03763764 T DK03763764 T DK 03763764T DK 1521831 T3 DK1521831 T3 DK 1521831T3
- Authority
- DK
- Denmark
- Prior art keywords
- molecules
- amino acids
- terminal amino
- alzheimer
- tau
- Prior art date
Links
- 241001465754 Metazoa Species 0.000 title 1
- 102000013498 tau Proteins Human genes 0.000 title 1
- 108010026424 tau Proteins Proteins 0.000 title 1
- 230000009261 transgenic effect Effects 0.000 title 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 abstract 2
- 102000029749 Microtubule Human genes 0.000 abstract 2
- 108091022875 Microtubule Proteins 0.000 abstract 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 abstract 2
- 210000005013 brain tissue Anatomy 0.000 abstract 2
- 210000004688 microtubule Anatomy 0.000 abstract 2
- 238000003556 assay Methods 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- 230000001575 pathological effect Effects 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/15—Humanized animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0312—Animal model for Alzheimer's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2821—Alzheimer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Neurology (AREA)
- Veterinary Medicine (AREA)
- Environmental Sciences (AREA)
- Analytical Chemistry (AREA)
- Toxicology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Biophysics (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Husbandry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT10532002 | 2002-07-12 | ||
PCT/EP2003/007390 WO2004007722A2 (en) | 2002-07-12 | 2003-07-09 | Transgenic animal expressing alzheimer’s tau protein |
Publications (1)
Publication Number | Publication Date |
---|---|
DK1521831T3 true DK1521831T3 (da) | 2008-06-30 |
Family
ID=30120907
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK03763763T DK1521774T3 (da) | 2002-07-12 | 2003-07-09 | Trunkerede Tau-proteiner |
DK03763764T DK1521831T3 (da) | 2002-07-12 | 2003-07-09 | Transgent dyr der udtrykker trunkeret alzheimers tauprotein |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK03763763T DK1521774T3 (da) | 2002-07-12 | 2003-07-09 | Trunkerede Tau-proteiner |
Country Status (10)
Country | Link |
---|---|
US (5) | US8288608B2 (ja) |
EP (3) | EP1521831B1 (ja) |
JP (3) | JP4414332B2 (ja) |
CN (2) | CN100572392C (ja) |
AT (2) | ATE391781T1 (ja) |
AU (2) | AU2003246664B2 (ja) |
DE (2) | DE60320258T2 (ja) |
DK (2) | DK1521774T3 (ja) |
ES (2) | ES2311734T3 (ja) |
WO (2) | WO2004007722A2 (ja) |
Families Citing this family (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK1521774T3 (da) * | 2002-07-12 | 2008-10-27 | Axon Neuroscience | Trunkerede Tau-proteiner |
DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
US7609947B2 (en) | 2004-09-10 | 2009-10-27 | Panasonic Corporation | Method and apparatus for coordinating playback from multiple video sources |
CN117903302A (zh) | 2005-11-30 | 2024-04-19 | Abbvie 公司 | 抗-Aβ球聚体抗体,其相关产品,生产所述抗体的方法,所述抗体的应用以及使用方法 |
PL1976877T5 (pl) | 2005-11-30 | 2017-09-29 | Abbvie Inc | Przeciwciała monoklonalne przeciwko białku amyloidu beta oraz ich zastosowania |
KR100734815B1 (ko) | 2006-02-15 | 2007-07-09 | 대한민국 | Htau24 유전자를 발현하는 형질전환 치매 마우스 및 그제조방법 |
US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
EP2486928A1 (en) | 2007-02-27 | 2012-08-15 | Abbott GmbH & Co. KG | Method for the treatment of amyloidoses |
CA2796339C (en) | 2010-04-15 | 2020-03-31 | Abbott Laboratories | Amyloid-beta binding proteins |
CA2808187A1 (en) | 2010-08-14 | 2012-02-23 | Abbvie Inc. | Amyloid-beta binding proteins |
CN102058619A (zh) * | 2010-12-08 | 2011-05-18 | 山西医科大学 | 一种阿尔茨海默病复合动物模型的制备方法 |
AU2011352333B2 (en) * | 2010-12-31 | 2016-12-08 | Zeus Scientific, Inc. | Improved methods for determining cell viability using molecular nucleic acid-based techniques |
EP2670434B1 (en) * | 2011-01-31 | 2018-12-26 | Tau Bio-Logic Corp. | Treatment of tauopathies |
WO2012162179A1 (en) | 2011-05-20 | 2012-11-29 | Oligomerix, Inc. | Tau protease compositions and methods of use |
HUE036177T2 (hu) | 2011-09-19 | 2018-06-28 | Axon Neuroscience Se | TAU-mediált patológia protein alapú terápiája és diagnózisa Alzheimer-betegségben |
WO2014008404A1 (en) | 2012-07-03 | 2014-01-09 | Washington University | Antibodies to tau |
KR102076384B1 (ko) | 2012-08-16 | 2020-02-11 | 아이피어리언 인코포레이티드 | 타우병증을 치료하는 방법 |
US9200068B2 (en) | 2012-12-18 | 2015-12-01 | Regents Of The University Of Minnesota | Compositions and methods related to tauopathy |
US8980270B2 (en) | 2013-01-18 | 2015-03-17 | Ipierian, Inc. | Methods of treating a tauopathy |
EP3104870A4 (en) | 2014-02-14 | 2017-09-13 | Ipierian, Inc. | Tau peptides, anti-tau antibodies, and methods of use thereof |
WO2015165961A1 (en) | 2014-04-29 | 2015-11-05 | Affiris Ag | Treatment and prevention of alzheimer's disease (ad) |
TW202136296A (zh) | 2014-06-27 | 2021-10-01 | 美商C2N醫療診斷有限責任公司 | 人類化抗-tau抗體 |
HUE053239T2 (hu) | 2014-11-19 | 2021-06-28 | Axon Neuroscience Se | Humanizált tau-ellenanyagok Alzheimer-kór kezelésére |
AU2016215155A1 (en) * | 2015-02-04 | 2017-08-17 | F. Hoffmann-La Roche Ag | Tau antisense oligomers and uses thereof |
WO2017172764A1 (en) * | 2016-04-01 | 2017-10-05 | The Regents Of The University Of California | Modified cell line and method of determining tauopathies |
KR101997319B1 (ko) | 2016-06-21 | 2019-07-08 | 전남대학교산학협력단 | 이형태체 항원인식 항체 생산을 유도하는 플라젤린 백신보조제 기반의 백신의 제조 및 그 응용 |
CA3047132A1 (en) * | 2016-12-30 | 2018-07-05 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods for the detection of tau protein aggregates |
EP3599842A4 (en) * | 2017-03-21 | 2020-12-30 | The Jackson Laboratory | GENETICALLY MODIFIED MOUSE EXPRESSING HUMAN APOE4 AND TREM.P.R47H AND ASSOCIATED PROCEDURES FOR USE |
BR112020018868A2 (pt) | 2018-03-28 | 2021-01-26 | Axon Neuroscience Se | métodos baseados em anticorpo para detectar e tratar doença de alzheimer |
US11155609B2 (en) | 2019-04-05 | 2021-10-26 | TauC3 Biologies Limited | Anti-TAUC3 antibodies and uses thereof |
AU2020325770B2 (en) | 2019-08-06 | 2022-08-25 | Aprinoia Therapeutics Limited | Antibodies that bind to pathological tau species and uses thereof |
CN110679549B (zh) * | 2019-11-05 | 2021-08-20 | 南通大学 | 一种阿尔茨海默病小鼠模型的构建方法 |
WO2023049871A2 (en) * | 2021-09-24 | 2023-03-30 | Alnylam Pharmaceuticals, Inc. | Microtubule associated protein tau (mapt) irna agent compositions and methods of use thereof |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06239899A (ja) | 1993-02-12 | 1994-08-30 | Teijin Ltd | ヒトタウ蛋白に対する抗体、並びに該抗体を利用する体液中のヒトタウ蛋白の測定方法 |
GB9506197D0 (en) * | 1995-03-27 | 1995-05-17 | Hoffmann La Roche | Inhibition of tau-tau association. |
WO1999062548A1 (en) | 1998-06-01 | 1999-12-09 | Advanced Research And Technology Institute | Methods and compositions for diagnosing tauopathies |
AU782281B2 (en) * | 1999-07-02 | 2005-07-14 | Janssen Pharmaceutica N.V. | Transgenic animals as models for neurodegenerative disease |
ATE326700T1 (de) * | 1999-09-09 | 2006-06-15 | Max Planck Gesellschaft | SCREENING NACH INHIBITOREN VON ßGEPAARTEN HELIKALEN FILAMENTENß |
WO2001053340A2 (en) * | 2000-01-21 | 2001-07-26 | Pharmacia & Upjohn Company | Transgenic mouse model of human neurodegenerative disease |
WO2001065252A1 (en) * | 2000-02-29 | 2001-09-07 | The Nathan S. Kline Institute For Psychiatric Research | Transgenic mice comprising a genomic human tau transgene |
GB0100119D0 (en) * | 2001-01-03 | 2001-02-14 | Univ Aberdeen | Materials and methods relating to protein aggregation in neurodegenerative disease |
GB0101049D0 (en) * | 2001-01-15 | 2001-02-28 | Univ Aberdeen | Materials and methods relating to protein aggregation in neurodegenerative disease |
AT500379B8 (de) * | 2001-02-02 | 2009-08-15 | Axon Neuroscience | Tau-proteine |
US20020164657A1 (en) * | 2001-02-23 | 2002-11-07 | Sharma Satish K. | Assays for assessing A beta-Tau aggregation |
DK1521774T3 (da) * | 2002-07-12 | 2008-10-27 | Axon Neuroscience | Trunkerede Tau-proteiner |
-
2003
- 2003-07-09 DK DK03763763T patent/DK1521774T3/da active
- 2003-07-09 CN CNB03816647XA patent/CN100572392C/zh not_active Expired - Lifetime
- 2003-07-09 EP EP03763764A patent/EP1521831B1/en not_active Expired - Lifetime
- 2003-07-09 AT AT03763764T patent/ATE391781T1/de active
- 2003-07-09 JP JP2004520542A patent/JP4414332B2/ja not_active Expired - Lifetime
- 2003-07-09 AT AT03763763T patent/ATE406383T1/de active
- 2003-07-09 AU AU2003246664A patent/AU2003246664B2/en not_active Expired
- 2003-07-09 DE DE60320258T patent/DE60320258T2/de not_active Expired - Lifetime
- 2003-07-09 DE DE60323231T patent/DE60323231D1/de not_active Expired - Lifetime
- 2003-07-09 CN CN03816645A patent/CN100577803C/zh not_active Expired - Lifetime
- 2003-07-09 US US10/521,049 patent/US8288608B2/en not_active Expired - Lifetime
- 2003-07-09 WO PCT/EP2003/007390 patent/WO2004007722A2/en active IP Right Grant
- 2003-07-09 JP JP2004520541A patent/JP4308760B2/ja not_active Expired - Fee Related
- 2003-07-09 EP EP03763763A patent/EP1521774B1/en not_active Expired - Lifetime
- 2003-07-09 EP EP08014706A patent/EP1995255A1/en not_active Withdrawn
- 2003-07-09 WO PCT/EP2003/007389 patent/WO2004007547A2/en active IP Right Grant
- 2003-07-09 ES ES03763763T patent/ES2311734T3/es not_active Expired - Lifetime
- 2003-07-09 AU AU2003253044A patent/AU2003253044B2/en not_active Expired
- 2003-07-09 ES ES03763764T patent/ES2304146T3/es not_active Expired - Lifetime
- 2003-07-09 DK DK03763764T patent/DK1521831T3/da active
- 2003-07-09 US US10/521,140 patent/US20060167227A1/en not_active Abandoned
-
2008
- 2008-12-02 JP JP2008307564A patent/JP2009143906A/ja active Pending
-
2009
- 2009-10-06 US US12/574,414 patent/US9485972B2/en active Active
-
2012
- 2012-09-14 US US13/618,946 patent/US9161520B2/en not_active Expired - Fee Related
-
2015
- 2015-09-10 US US14/850,683 patent/US20160106077A1/en not_active Abandoned
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