FI112095B - Ei-radioaktiivinen liuoshybridisaatiomenetelmä ja -kitti - Google Patents
Ei-radioaktiivinen liuoshybridisaatiomenetelmä ja -kitti Download PDFInfo
- Publication number
- FI112095B FI112095B FI942239A FI942239A FI112095B FI 112095 B FI112095 B FI 112095B FI 942239 A FI942239 A FI 942239A FI 942239 A FI942239 A FI 942239A FI 112095 B FI112095 B FI 112095B
- Authority
- FI
- Finland
- Prior art keywords
- sample
- probe
- dna
- nucleic acid
- hybrid
- Prior art date
Links
Classifications
-
- 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
- C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
- C12Q1/701—Specific hybridization probes
- C12Q1/706—Specific hybridization probes for hepatitis
-
- 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
- C12Q1/6813—Hybridisation assays
-
- 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
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
-
- 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
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6865—Promoter-based amplification, e.g. nucleic acid sequence amplification [NASBA], self-sustained sequence replication [3SR] or transcription-based amplification system [TAS]
-
- 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
- C12Q1/6888—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
- C12Q1/689—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
-
- 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
- C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
- C12Q1/701—Specific hybridization probes
- C12Q1/708—Specific hybridization probes for papilloma
-
- 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
- C12Q2525/00—Reactions involving modified oligonucleotides, nucleic acids, or nucleotides
- C12Q2525/30—Oligonucleotides characterised by their secondary structure
- C12Q2525/301—Hairpin oligonucleotides
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79258591A | 1991-11-14 | 1991-11-14 | |
| US79258591 | 1991-11-14 | ||
| PCT/US1992/009604 WO1993010263A1 (fr) | 1991-11-14 | 1992-11-12 | Kit et dosage par hybridation non radioactive |
| US9209604 | 1992-11-12 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI942239A0 FI942239A0 (fi) | 1994-05-13 |
| FI942239L FI942239L (fi) | 1994-07-06 |
| FI112095B true FI112095B (fi) | 2003-10-31 |
Family
ID=25157398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI942239A FI112095B (fi) | 1991-11-14 | 1994-05-13 | Ei-radioaktiivinen liuoshybridisaatiomenetelmä ja -kitti |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US6228578B1 (fr) |
| EP (1) | EP0667918B1 (fr) |
| JP (1) | JP3091492B2 (fr) |
| AT (1) | ATE189831T1 (fr) |
| AU (1) | AU673813B2 (fr) |
| DE (1) | DE69230693T2 (fr) |
| DK (1) | DK0667918T3 (fr) |
| ES (1) | ES2145750T3 (fr) |
| FI (1) | FI112095B (fr) |
| GR (1) | GR3033345T3 (fr) |
| WO (1) | WO1993010263A1 (fr) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5981179A (en) * | 1991-11-14 | 1999-11-09 | Digene Diagnostics, Inc. | Continuous amplification reaction |
| BR9814272A (pt) * | 1997-12-12 | 2000-10-03 | Digene Corp | Meio de coleta universal |
| US6225053B1 (en) * | 1997-12-12 | 2001-05-01 | Digene Corporation | Detection of hepatitis B virus |
| US5994079A (en) | 1998-02-06 | 1999-11-30 | Digene Corporation | Direct detection of RNA mediated by reverse transcriptase lacking RNAse H function |
| US6686151B1 (en) * | 1998-02-06 | 2004-02-03 | Digene Corporation | Immunological detection of RNA:DNA hybrids on microarrays |
| US7399589B2 (en) | 1998-02-06 | 2008-07-15 | Digene Corporation | Immunological detection of RNA:DNA hybrids on microarrays |
| ATE317297T1 (de) * | 1998-11-23 | 2006-02-15 | Us Gov Sec Army | Reinigungsmethode und vorrichtung |
| US6723505B1 (en) * | 1999-08-13 | 2004-04-20 | Nye Colifast As | Method for identification of the indicators of contamination in liquid samples |
| US20040115692A1 (en) * | 2000-04-03 | 2004-06-17 | Cytyc Corporation | Methods, compositions and apparatuses for detecting a target in a preservative solution |
| US7439016B1 (en) | 2000-06-15 | 2008-10-21 | Digene Corporation | Detection of nucleic acids by type-specific hybrid capture method |
| US7601497B2 (en) * | 2000-06-15 | 2009-10-13 | Qiagen Gaithersburg, Inc. | Detection of nucleic acids by target-specific hybrid capture method |
| US7494817B2 (en) * | 2000-09-06 | 2009-02-24 | Transnet Yx, Inc. | Methods for genotype screening using magnetic particles |
| DK1337547T3 (da) * | 2000-11-03 | 2014-06-10 | Isis Pharmaceuticals Inc | Nuklease-baseret fremgangsmåde til detektion og kvantificering af oligonukleotider |
| US9261460B2 (en) | 2002-03-12 | 2016-02-16 | Enzo Life Sciences, Inc. | Real-time nucleic acid detection processes and compositions |
| CA2356540A1 (fr) * | 2001-08-30 | 2003-02-28 | Emory University | Sequences d'adn exprimees jouant un role dans les fonctions mitochondriales |
| US20050123913A1 (en) * | 2001-08-30 | 2005-06-09 | Emory University | Human mitochondrial dna polymorphisms, haplogroups, associations with physiological conditions, and genotyping arrays |
| KR20030049802A (ko) * | 2001-12-17 | 2003-06-25 | 권윤정 | 바이오 칩에서 프로브와 시료 핵산의 혼성화 여부를 효소반응으로 구별하는 방법 |
| US9353405B2 (en) | 2002-03-12 | 2016-05-31 | Enzo Life Sciences, Inc. | Optimized real time nucleic acid detection processes |
| US7166478B2 (en) * | 2002-03-12 | 2007-01-23 | Enzo Life Sciences, Inc., C/O Enzo Biochem, Inc. | Labeling reagents and labeled targets, target labeling processes and other processes for using same in nucleic acid determinations and analyses |
| US20030175828A1 (en) * | 2002-03-15 | 2003-09-18 | Lazar James G. | Signal amplification by Hybrid Capture |
| US20030224370A1 (en) * | 2002-05-31 | 2003-12-04 | William Rassman | Method and apparatus for recognizing molecular compounds |
| CA2506129C (fr) | 2002-11-15 | 2015-02-17 | Idenix (Cayman) Limited | Nucleoside a ramification en 2' et mutation de flaviviridae |
| JP2007528692A (ja) * | 2003-05-28 | 2007-10-18 | メイバン・テクノロジーズ・エルエルシー | 分子化合物を認識する方法及び装置 |
| US20060161076A1 (en) * | 2005-01-06 | 2006-07-20 | Diamics, Inc. | Systems and methods for collection of cell clusters |
| US20060189893A1 (en) * | 2005-01-06 | 2006-08-24 | Diamics, Inc. | Systems and methods for detecting abnormal cells |
| WO2006096727A2 (fr) * | 2005-03-07 | 2006-09-14 | Cellay Llc | Procede permettant de detecter l'adn integre |
| US20070037174A1 (en) * | 2005-08-12 | 2007-02-15 | Rampal Jang B | Chemiluminescent generated fluorescent labeling |
| US7732166B2 (en) * | 2005-11-15 | 2010-06-08 | Oncohealth Corporation | Detection method for human pappilomavirus (HPV) and its application in cervical cancer |
| US7972776B2 (en) * | 2005-11-15 | 2011-07-05 | Oncohealth Corporation | Protein chips for HPV detection |
| US20080125333A1 (en) * | 2006-05-31 | 2008-05-29 | Antara Biosciences Inc. | Devices and kits for detecting one or more target agents |
| US8968995B2 (en) * | 2008-11-12 | 2015-03-03 | Oncohealth Corp. | Detection, screening, and diagnosis of HPV-associated cancers |
| US20100003704A1 (en) | 2008-06-13 | 2010-01-07 | Shuling Cheng | IN SITU detection of early stages and late stages HPV infection |
| WO2008103015A1 (fr) * | 2007-02-23 | 2008-08-28 | Panagene Inc. | Procédés, compositions et kits destinés à augmenter l'efficacité ou la spécificité d'une hybridation mise en oeuvre entre des sondes pna immobilisées sur un support et des acides nucléiques cibles |
| WO2009129505A2 (fr) * | 2008-04-17 | 2009-10-22 | Qiagen Gaithersburg, Inc. | Compositions, procédé et trousses utilisant des sondes synthétiques pour déterminer la présence d'un acide nucléique voulu |
| WO2009129558A1 (fr) | 2008-04-24 | 2009-10-29 | Newsouth Innovations Pty Limited | Groupes de gènes codant pour la saxitoxine des cyanobactéries et détection d'organismes cyanotoxiques |
| WO2010062546A1 (fr) * | 2008-10-27 | 2010-06-03 | Qiagen Gaithersburg Inc. | Essai de capture d’hybride à résultats rapides sur une plate-forme automatisée |
| US8325494B2 (en) | 2009-01-05 | 2012-12-04 | Afl Telecommunications Llc | Universal mounting bracket |
| EP2385979B1 (fr) * | 2009-01-28 | 2017-08-16 | QIAGEN Gaithersburg, Inc. | Procédé de préparation d'un échantillon de grand volume spécifique à une séquence et dosage |
| WO2010127228A1 (fr) | 2009-05-01 | 2010-11-04 | Qiagen Gaithersburg, Inc. | Procédé d'amplification non ciblée pour la détection de formes d'épissage d'arn dans un échantillon |
| JP2012526286A (ja) | 2009-05-07 | 2012-10-25 | オンコヘルス コーポレーション | ヒトパピローマウイルス(hpv)およびhpv関連癌の初期段階および後期段階の検出、スクリーニング、および診断のための高度または≧cin2の同定 |
| WO2011032124A1 (fr) | 2009-09-14 | 2011-03-17 | Qiagen Gaithersburg, Inc. | Compositions et méthodes pour la récupération d'acides nucléiques ou de protéines à partir d'échantillons de tissus fixés dans des milieux de cytologie |
| JP5819851B2 (ja) | 2010-01-08 | 2015-11-24 | オンコヘルス コーポレーション | Hpv関連の癌の治療及びスクリーニングのための細胞に基づいた高処理能力hpv免疫アッセイ |
| WO2011094514A1 (fr) | 2010-01-29 | 2011-08-04 | Qiagen Gaithersburg, Inc. | Procédés et compositions pour la purification et l'analyse multiplexée d'acides nucléiques séquence-spécifique |
| AU2011210748A1 (en) | 2010-01-29 | 2012-08-09 | Qiagen Gaithersburg, Inc. | Method of determining and confirming the presence of HPV in a sample |
| JP5726917B2 (ja) * | 2010-02-26 | 2015-06-03 | ヴェンタナ メディカル システムズ, インク. | ポリタグプローブ |
| AU2011255638B2 (en) | 2010-05-19 | 2016-08-25 | Qiagen Gaithersburg, Inc. | Methods and compositions for sequence-specific purification and multiplex analysis of nucleic acids |
| JP6153866B2 (ja) | 2010-05-25 | 2017-06-28 | キアゲン ガイサーズバーグ アイエヌシー. | 迅速なハイブリッド捕捉アッセイ、及び関連する戦略的に切断されたプローブ |
| CN103597095B (zh) | 2011-02-24 | 2016-08-17 | 奇亚根盖瑟斯堡股份有限公司 | 用于检测hpv核酸的材料和方法 |
| AU2012332215B2 (en) | 2011-11-03 | 2018-01-18 | Qiagen Gaithersburg, Inc. | Materials and method for immobilizing, isolating, and concentrating cells using carboxylated surfaces |
| USRE48665E1 (en) | 2014-02-28 | 2021-08-03 | Gen-Probe Incorporated | Method of isolating nucleic acid from specimens in liquid-based cytology preservatives containing formaldehyde |
| GB2528344B (en) | 2014-02-28 | 2018-10-31 | Gen Probe Inc | Method of isolating nucleic acid from specimens in liquid-based cytology preservatives containing formaldehyde |
| US10356478B2 (en) * | 2015-01-08 | 2019-07-16 | The Directv Group, Inc. | Systems and methods for spotted advertising and control of corresponding user interfaces and transactions via user receiving devices and mobile devices |
| JP7056143B2 (ja) * | 2016-12-27 | 2022-04-19 | 東洋紡株式会社 | 免疫学的測定用組成物および免疫学的測定方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4732847A (en) | 1981-06-09 | 1988-03-22 | University Of Hawaii | Monoclonal antibodies for DNA-RNA hybrid complexes and their uses |
| US4623627A (en) | 1983-08-19 | 1986-11-18 | Cetus Corporation | Monoclonal antibody having specificity for the double-stranded conformation of native DNA and diagnostic methods using same |
| US4743535A (en) | 1984-11-07 | 1988-05-10 | Miles Inc. | Hybridization assay employing labeled probe and anti-hybrid |
| EP0146039A3 (fr) * | 1983-12-12 | 1986-08-27 | Miles Inc. | Test d'hybridation avec immobilisation d'hybrides par liaison antihybride |
| ZA853756B (en) | 1984-06-01 | 1986-01-29 | Miles Lab | Nucleic acid hybridization assay employing immobilized rna probes |
| CA1253777A (fr) | 1984-06-01 | 1989-05-09 | Robert J. Carrico | Essai d'hybridation de l'acide nucleique au moyen de sondes arn immobilisees |
| US4563417A (en) | 1984-08-31 | 1986-01-07 | Miles Laboratories, Inc. | Nucleic acid hybridization assay employing antibodies to intercalation complexes |
| US4965188A (en) * | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
| AU558846B2 (en) * | 1985-06-21 | 1987-02-12 | Miles Laboratories Inc. | Solid-phase hydridization assay using anti-hybrid antibodies |
| US4968602A (en) * | 1986-03-05 | 1990-11-06 | Molecular Diagnostics, Inc. | Solution-phase single hybridization assay for detecting polynucleotide sequences |
| GB8712646D0 (en) * | 1987-05-29 | 1987-07-01 | Clayton Found Res | Structural evidence |
| JPH03503476A (ja) * | 1987-07-22 | 1991-08-08 | インペリアル キャンサー リサーチ テクノロジー,リミテッド | 消化方法 |
-
1992
- 1992-11-12 DE DE69230693T patent/DE69230693T2/de not_active Expired - Lifetime
- 1992-11-12 WO PCT/US1992/009604 patent/WO1993010263A1/fr active IP Right Grant
- 1992-11-12 EP EP92924354A patent/EP0667918B1/fr not_active Expired - Lifetime
- 1992-11-12 AU AU30689/92A patent/AU673813B2/en not_active Expired
- 1992-11-12 AT AT92924354T patent/ATE189831T1/de active
- 1992-11-12 ES ES92924354T patent/ES2145750T3/es not_active Expired - Lifetime
- 1992-11-12 DK DK92924354T patent/DK0667918T3/da active
- 1992-11-12 JP JP05509340A patent/JP3091492B2/ja not_active Expired - Lifetime
-
1994
- 1994-01-18 US US08/183,154 patent/US6228578B1/en not_active Expired - Lifetime
- 1994-05-13 FI FI942239A patent/FI112095B/fi not_active IP Right Cessation
-
2000
- 2000-04-26 GR GR20000401030T patent/GR3033345T3/el unknown
-
2001
- 2001-05-07 US US09/850,041 patent/US20020012936A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DE69230693T2 (de) | 2000-06-15 |
| EP0667918A1 (fr) | 1995-08-23 |
| AU3068992A (en) | 1993-06-15 |
| FI942239L (fi) | 1994-07-06 |
| EP0667918B1 (fr) | 2000-02-16 |
| ATE189831T1 (de) | 2000-03-15 |
| WO1993010263A1 (fr) | 1993-05-27 |
| ES2145750T3 (es) | 2000-07-16 |
| FI942239A0 (fi) | 1994-05-13 |
| US6228578B1 (en) | 2001-05-08 |
| GR3033345T3 (en) | 2000-09-29 |
| JPH07505759A (ja) | 1995-06-29 |
| DK0667918T3 (da) | 2000-06-05 |
| JP3091492B2 (ja) | 2000-09-25 |
| AU673813B2 (en) | 1996-11-28 |
| US20020012936A1 (en) | 2002-01-31 |
| DE69230693D1 (de) | 2000-03-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |