ZA9811619B - Uses of bacteria endowed with arginine deiminase and compositions containing such bacteria - Google Patents
Uses of bacteria endowed with arginine deiminase and compositions containing such bacteriaInfo
- Publication number
- ZA9811619B ZA9811619B ZA9811619A ZA9811619A ZA9811619B ZA 9811619 B ZA9811619 B ZA 9811619B ZA 9811619 A ZA9811619 A ZA 9811619A ZA 9811619 A ZA9811619 A ZA 9811619A ZA 9811619 B ZA9811619 B ZA 9811619B
- Authority
- ZA
- South Africa
- Prior art keywords
- bacteria
- compositions containing
- endowed
- arginine deiminase
- deiminase
- Prior art date
Links
Classifications
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/225—Lactobacillus
- C12R2001/24—Lactobacillus brevis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT98RM000103A IT1298918B1 (it) | 1998-02-20 | 1998-02-20 | Uso di batteri dotati di arginina deiminasi per indurre apoptosi e/o ridurre una reazione infiammatoria e composizioni farmaceutiche |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA9811619B true ZA9811619B (en) | 1999-06-23 |
Family
ID=11405583
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA9811619A ZA9811619B (en) | 1998-02-20 | 1998-12-18 | Uses of bacteria endowed with arginine deiminase and compositions containing such bacteria |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US6572854B1 (es) |
| EP (1) | EP1058725B1 (es) |
| JP (1) | JP4253439B2 (es) |
| KR (1) | KR100594569B1 (es) |
| CN (1) | CN1189560C (es) |
| AR (2) | AR020053A1 (es) |
| AT (1) | ATE391774T1 (es) |
| AU (1) | AU754483B2 (es) |
| BR (1) | BR9815677A (es) |
| CA (1) | CA2321263C (es) |
| CY (1) | CY1108112T1 (es) |
| DE (1) | DE69839351T2 (es) |
| DK (1) | DK1058725T3 (es) |
| EA (1) | EA006018B1 (es) |
| ES (1) | ES2303357T3 (es) |
| HK (1) | HK1033338A1 (es) |
| IL (1) | IL137799A (es) |
| IN (2) | IN1999KO00116A (es) |
| IT (1) | IT1298918B1 (es) |
| MX (1) | MX237377B (es) |
| PT (1) | PT1058725E (es) |
| SI (1) | SI1058725T1 (es) |
| TR (1) | TR200002326T2 (es) |
| WO (1) | WO1999042568A1 (es) |
| ZA (1) | ZA9811619B (es) |
Families Citing this family (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1296148B1 (it) * | 1996-11-22 | 1999-06-09 | Renata Maria Anna Ve Cavaliere | Uso di batteri lattici per accrescere il livello delle ceramidi della pelle e delle mucose, e composizioni dermatologiche e cosmetiche atte |
| IT1311495B1 (it) * | 1999-06-09 | 2002-03-13 | Mendes S U R L | Composizione comprendente sfingomielinasi alcalina, utilizzabile qualeprodotto dietetico, integratore alimentare o medicamento. |
| US8697051B2 (en) * | 1999-06-09 | 2014-04-15 | Vsl Pharmaceuticals Inc. | Composition comprising alkaline sphingomyelinase for use as a dietetic preparation, food supplement or pharmaceutical product |
| IT1306716B1 (it) * | 1999-06-21 | 2001-10-02 | Mendes S U R L | Associazione di batteri lattici e suo uso per la prevenzione e/o iltrattamento terapeutico di infezioni e di stati infiammatori. |
| AUPQ415899A0 (en) * | 1999-11-19 | 1999-12-16 | Vasse Research Institute Pty Ltd | Compositions for and methods of treatment of allergic diseases |
| HU227086B1 (en) * | 1999-11-25 | 2010-06-28 | Vakcina Kft | Lactobacillus vaccine for treating prostata inflammatory and benign prostata hyperplasia |
| FR2809312B1 (fr) * | 2000-05-25 | 2002-07-12 | Gervais Danone Sa | Utilisation de l. casei dans des compositions immunostimulantes |
| US6767537B2 (en) * | 2000-05-26 | 2004-07-27 | Phil Arnold Nicolay | Composition and method for the treatment of sinusitis |
| MXPA04001999A (es) * | 2001-09-05 | 2004-07-16 | Vsl Pharmaceuticals Inc | Bacterias de acido lactico que comprende dinucleotidos de citosina-guanina no metilados para usarse en terapia. |
| ITRM20010763A1 (it) * | 2001-12-21 | 2003-06-21 | Simone Claudio De | Nuovo ceppo di batterio lattico e composizioni commestibili, farmaci e prodotti veterinari che lo contengono. |
| JP4733393B2 (ja) * | 2002-11-18 | 2011-07-27 | ポラリス・グループ | インビボでウイルス複製を阻害する方法 |
| US20050158294A1 (en) | 2003-12-19 | 2005-07-21 | The Procter & Gamble Company | Canine probiotic Bifidobacteria pseudolongum |
| US8877178B2 (en) | 2003-12-19 | 2014-11-04 | The Iams Company | Methods of use of probiotic bifidobacteria for companion animals |
| TW200700074A (en) * | 2005-03-04 | 2007-01-01 | Calpis Co Ltd | Inducer of t cell apoptosis |
| DK1880001T3 (da) | 2005-05-31 | 2011-09-12 | Iams Company | Feline probiotiske lactobacilli |
| EP1885383B1 (en) | 2005-05-31 | 2016-09-21 | IAMS Europe B.V. | Feline probiotic bifidobacteria |
| CN101668534B (zh) | 2006-12-21 | 2013-05-22 | 卡尔皮斯株式会社 | IgA产生促进剂 |
| CN100584940C (zh) * | 2007-05-17 | 2010-01-27 | 江南大学 | 一株产精氨酸脱亚氨酶的菌种及其应用 |
| JP5247120B2 (ja) * | 2007-11-02 | 2013-07-24 | 雪印メグミルク株式会社 | Ｌ−オルニチン含有物の製造方法 |
| EE05341B1 (et) * | 2008-05-13 | 2010-08-16 | O� Tervisliku Piima Biotehnoloogiate Arenduskeskus | Isoleeritud mikroorganismi tvi Lactobacillus plantarum Inducia DSM 21379 kui organismi loomulikku kaitsev?imet t?stev probiootik, seda sisaldav toiduaine ja kompositsioon ning mikroorganismi kasutamine rakulist immuunsust t?stva ravimi valmistamisek |
| US9771199B2 (en) | 2008-07-07 | 2017-09-26 | Mars, Incorporated | Probiotic supplement, process for making, and packaging |
| CN101606952B (zh) * | 2008-06-17 | 2012-09-19 | 上海交通大学医学院附属第三人民医院 | 乳双歧杆菌在制备预防泌尿系统结石药物中的应用 |
| JP5526320B2 (ja) * | 2008-09-04 | 2014-06-18 | 国立大学法人旭川医科大学 | 腸管保護剤 |
| US10104903B2 (en) | 2009-07-31 | 2018-10-23 | Mars, Incorporated | Animal food and its appearance |
| JP5820725B2 (ja) * | 2009-10-22 | 2015-11-24 | 株式会社ヤクルト本社 | がん発症リスク低減剤 |
| WO2011125619A1 (ja) | 2010-04-08 | 2011-10-13 | 国立大学法人旭川医科大学 | 腸管保護剤 |
| KR101062779B1 (ko) | 2010-04-28 | 2011-09-06 | 삼육대학교산학협력단 | 충치 유발 세균의 성장 억제 활성을 나타내는 비피도박테리움 아돌레센티스 ｓｐｍ1005 균주 및 상기 비피도박테리움 아돌레센티스 ｓｐｍ1005 균주 또는 이의 배양물을 유효 성분으로 하는 충치 예방용 식품 및 약제학 조성물 |
| GB201112091D0 (en) | 2011-07-14 | 2011-08-31 | Gt Biolog Ltd | Bacterial strains isolated from pigs |
| GB201117313D0 (en) | 2011-10-07 | 2011-11-16 | Gt Biolog Ltd | Bacterium for use in medicine |
| CN102433290B (zh) * | 2012-01-16 | 2013-06-12 | 江南大学 | 一株产瓜氨酸的菌株及用该菌株生物合成瓜氨酸的方法 |
| EP3782653A1 (en) | 2012-04-04 | 2021-02-24 | Polaris Group | Composition comprising pegylated arginine deiminase |
| EP2968482B1 (en) | 2013-03-15 | 2020-05-06 | TDW Group | Arginine deiminase with reduced cross-reactivity toward adi - peg 20 antibodies for cancer treatment |
| GB201306536D0 (en) | 2013-04-10 | 2013-05-22 | Gt Biolog Ltd | Polypeptide and immune modulation |
| CN107172883A (zh) * | 2014-01-22 | 2017-09-15 | 株式会社明治 | 瓜氨酸的制备方法 |
| SG11201607736UA (en) | 2014-03-18 | 2016-10-28 | Tdw Group | Engineered chimeric pegylated adi and methods of use |
| CN114522225A (zh) | 2014-09-16 | 2022-05-24 | 瑞华药业集团 | 用于癌症治疗的对adi-peg20抗体具有降低的交叉反应性的精氨酸脱亚氨酶 |
| KR101942955B1 (ko) | 2014-12-23 | 2019-01-28 | 4디 파마 리서치 리미티드 | 면역 조정 |
| EA035925B1 (ru) | 2014-12-23 | 2020-09-01 | 4Д Фарма Рисерч Лимитед | Полипептид и иммуномодуляция |
| MA41060B1 (fr) | 2015-06-15 | 2019-11-29 | 4D Pharma Res Ltd | Compositions comprenant des souches bactériennes |
| NZ777234A (en) | 2015-06-15 | 2022-02-25 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
| MA41010B1 (fr) | 2015-06-15 | 2020-01-31 | 4D Pharma Res Ltd | Compositions comprenant des souches bactériennes |
| EP3307288B1 (en) | 2015-06-15 | 2019-07-24 | 4D Pharma Research Limited | Compositions comprising bacterial strains |
| LT3240554T (lt) | 2015-06-15 | 2019-11-11 | 4D Pharma Res Ltd | Blautia stercosis ir wexlerae, skirtos naudoti uždegiminių ir autoimuninių ligų gydymui |
| GB201520497D0 (en) | 2015-11-20 | 2016-01-06 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
| ES2662617T3 (es) | 2015-11-20 | 2018-04-09 | 4D Pharma Research Limited | Composiciones que comprenden cepas bacterianas |
| GB201520631D0 (en) | 2015-11-23 | 2016-01-06 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
| GB201520638D0 (en) | 2015-11-23 | 2016-01-06 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
| CN106994134B (zh) * | 2016-01-25 | 2020-08-25 | 深圳华大生命科学研究院 | 肠道益生菌在预防和/或治疗糖尿病及其相关疾病中的应用 |
| GB201612191D0 (en) | 2016-07-13 | 2016-08-24 | 4D Pharma Plc | Compositions comprising bacterial strains |
| CN108883139B (zh) | 2016-03-04 | 2022-04-26 | 4D制药有限公司 | 包含细菌菌株的组合物 |
| TW201821093A (zh) | 2016-07-13 | 2018-06-16 | 英商４Ｄ製藥有限公司 | 包含細菌菌株之組合物 |
| GB201621123D0 (en) | 2016-12-12 | 2017-01-25 | 4D Pharma Plc | Compositions comprising bacterial strains |
| WO2018125735A1 (en) * | 2016-12-29 | 2018-07-05 | Kibow Biotech, Inc. | Composition and method for maintaining healthy kidney function |
| CN108265068B (zh) * | 2016-12-31 | 2021-06-15 | 江苏众红生物工程创药研究院有限公司 | 重组精氨酸脱亚胺酶及其产业化制备方法和应用 |
| CN110913878A (zh) | 2017-05-22 | 2020-03-24 | 4D制药研究有限公司 | 包含细菌菌株的组合物 |
| EP3630942B1 (en) | 2017-05-24 | 2022-11-30 | 4D Pharma Research Limited | Compositions comprising bacterial strain |
| DK3804737T3 (da) | 2017-06-14 | 2022-07-25 | 4D Pharma Res Ltd | Sammensætninger omfattende bakteriestammer |
| WO2018229189A1 (en) | 2017-06-14 | 2018-12-20 | 4D Pharma Research Limited | Compositions comprising bacterial strains |
| PT3638271T (pt) | 2017-06-14 | 2021-01-05 | 4D Pharma Res Ltd | Composições contendo estirpes bacterianas |
| RU2675110C1 (ru) * | 2018-04-09 | 2018-12-17 | Федеральное государственное бюджетное учреждение науки Институт общей генетики им. Н.И. Вавилова Российской академии наук (ИОГЕН РАН) | Фармацевтическая композиция для терапии воспалительных заболеваний слизистых оболочек кишечника на основе штамма Lactobacillus brevis 47f, проявляющая местную противовоспалительную активность |
| FR3082207B1 (fr) * | 2018-06-06 | 2022-03-25 | Agronomique Inst Nat Rech | Nouvelle souche probiotique de lactobacillus brevis |
| KR102069622B1 (ko) * | 2019-06-25 | 2020-01-23 | 한국식품연구원 | 락토바실러스 퍼멘텀 WiKim0102를 유효성분으로 포함하는 암의 예방 또는 치료용 약학 조성물 |
| JPWO2021261423A1 (es) * | 2020-06-22 | 2021-12-30 | ||
| KR102363111B1 (ko) * | 2021-06-29 | 2022-02-15 | (주)바이오일레븐 | 항염 및 항산화 활성을 갖는 락토바실러스 퍼멘텀 균주 및 이의 용도 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4415550A (en) * | 1983-03-04 | 1983-11-15 | Pakhomov Gennady N | Treatment-and-prophylactic tooth paste possessing anticarious effect |
| JP2900279B2 (ja) | 1989-08-02 | 1999-06-02 | 株式会社ジャパンエナジー | 新規なアルギニンデイミナーゼ、その製造法及び該酵素を有効成分とする制癌剤 |
| US5196195A (en) * | 1990-03-27 | 1993-03-23 | Cornell Research Foundation, Inc. | Use of arginase to control nitric oxide formation |
| GB9107305D0 (en) * | 1991-04-08 | 1991-05-22 | Unilever Plc | Probiotic |
| AUPM596894A0 (en) | 1994-05-30 | 1994-06-23 | Hybrid Scientific Pty Ltd | Composition for treating gastrointestinal disorders - a combination of bismuth salts plus lactobacillus or bifidobacteria species bacteria for treating gastrointestinal disorders |
| US5599795A (en) * | 1994-08-19 | 1997-02-04 | Mccann; Michael | Method for treatment of idiopathic inflammatory bowel disease (IIBD) |
-
1998
- 1998-02-20 IT IT98RM000103A patent/IT1298918B1/it active IP Right Grant
- 1998-10-13 CN CNB988137054A patent/CN1189560C/zh not_active Expired - Lifetime
- 1998-10-13 US US09/601,533 patent/US6572854B1/en not_active Expired - Lifetime
- 1998-10-13 KR KR20007008973A patent/KR100594569B1/ko not_active IP Right Cessation
- 1998-10-13 EA EA200000856A patent/EA006018B1/ru not_active IP Right Cessation
- 1998-10-13 ES ES98950301T patent/ES2303357T3/es not_active Expired - Lifetime
- 1998-10-13 SI SI9830908T patent/SI1058725T1/sl unknown
- 1998-10-13 AU AU96441/98A patent/AU754483B2/en not_active Expired
- 1998-10-13 DK DK98950301T patent/DK1058725T3/da active
- 1998-10-13 WO PCT/IT1998/000275 patent/WO1999042568A1/en active IP Right Grant
- 1998-10-13 AT AT98950301T patent/ATE391774T1/de active
- 1998-10-13 DE DE69839351T patent/DE69839351T2/de not_active Expired - Lifetime
- 1998-10-13 BR BR9815677-2A patent/BR9815677A/pt active Search and Examination
- 1998-10-13 EP EP98950301A patent/EP1058725B1/en not_active Expired - Lifetime
- 1998-10-13 CA CA002321263A patent/CA2321263C/en not_active Expired - Lifetime
- 1998-10-13 JP JP2000532508A patent/JP4253439B2/ja not_active Expired - Fee Related
- 1998-10-13 IL IL13779998A patent/IL137799A/xx not_active IP Right Cessation
- 1998-10-13 TR TR2000/02326T patent/TR200002326T2/xx unknown
- 1998-10-13 PT PT98950301T patent/PT1058725E/pt unknown
- 1998-12-18 ZA ZA9811619A patent/ZA9811619B/xx unknown
-
1999
- 1999-01-08 AR ARP990100064A patent/AR020053A1/es active IP Right Grant
- 1999-02-15 IN IN116KO1999 patent/IN1999KO00116A/en unknown
- 1999-02-15 IN IN117CA1999 patent/IN188450B/en unknown
-
2000
- 2000-08-16 MX MXPA00007990 patent/MX237377B/es active IP Right Grant
-
2001
- 2001-06-14 HK HK01104084A patent/HK1033338A1/xx not_active IP Right Cessation
-
2003
- 2003-03-28 US US10/400,675 patent/US7147847B2/en not_active Expired - Fee Related
-
2008
- 2008-06-03 CY CY20081100582T patent/CY1108112T1/el unknown
-
2009
- 2009-05-19 AR ARP090101791A patent/AR071841A2/es unknown
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