DK1140993T3 - Glycopeptidderivater og farmaceutiske præparater indeholdende dem - Google Patents
Glycopeptidderivater og farmaceutiske præparater indeholdende demInfo
- Publication number
- DK1140993T3 DK1140993T3 DK99965331T DK99965331T DK1140993T3 DK 1140993 T3 DK1140993 T3 DK 1140993T3 DK 99965331 T DK99965331 T DK 99965331T DK 99965331 T DK99965331 T DK 99965331T DK 1140993 T3 DK1140993 T3 DK 1140993T3
- Authority
- DK
- Denmark
- Prior art keywords
- pharmaceutical preparations
- preparations containing
- derivatives
- glycopeptide
- glycopeptide derivatives
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
- C07K9/006—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure
- C07K9/008—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure directly attached to a hetero atom of the saccharide radical, e.g. actaplanin, avoparcin, ristomycin, vancomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11372898P | 1998-12-23 | 1998-12-23 | |
| US12931399P | 1999-04-14 | 1999-04-14 | |
| US16402499P | 1999-11-04 | 1999-11-04 | |
| US16997899P | 1999-12-10 | 1999-12-10 | |
| PCT/US1999/030543 WO2000039156A1 (en) | 1998-12-23 | 1999-12-22 | Glycopeptide derivatives and pharmaceutical compositions containing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK1140993T3 true DK1140993T3 (da) | 2003-10-06 |
Family
ID=27493926
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK99965331T DK1140993T3 (da) | 1998-12-23 | 1999-12-22 | Glycopeptidderivater og farmaceutiske præparater indeholdende dem |
Country Status (23)
| Country | Link |
|---|---|
| US (9) | US6392012B1 (da) |
| EP (1) | EP1140993B1 (da) |
| JP (1) | JP4362017B2 (da) |
| KR (1) | KR100665204B1 (da) |
| CN (1) | CN1249081C (da) |
| AT (1) | ATE242783T1 (da) |
| AU (1) | AU768204B2 (da) |
| BR (1) | BRPI9914221B8 (da) |
| CA (1) | CA2336445C (da) |
| CZ (1) | CZ301184B6 (da) |
| DE (1) | DE69908819T2 (da) |
| DK (1) | DK1140993T3 (da) |
| ES (1) | ES2201825T3 (da) |
| HK (1) | HK1040721B (da) |
| HU (1) | HU230190B1 (da) |
| IL (2) | IL140093A0 (da) |
| NO (1) | NO326066B1 (da) |
| NZ (1) | NZ508594A (da) |
| PL (1) | PL198311B1 (da) |
| PT (1) | PT1140993E (da) |
| SI (1) | SI1140993T1 (da) |
| WO (1) | WO2000039156A1 (da) |
| ZA (1) | ZA200007222B (da) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2201825T3 (es) * | 1998-12-23 | 2004-03-16 | Theravance, Inc. | Derivados del glicopeptidos y composiciones farmaceuticas que los contienen. |
| US6699836B2 (en) * | 1999-04-02 | 2004-03-02 | The Trustees Of Princeton University | Vancomycin analogs |
| WO2000059528A1 (en) * | 1999-04-02 | 2000-10-12 | The Trustees Of Princeton University | Desleucyl glycopeptide antibiotics and methods of making same |
| WO2001057071A2 (en) * | 2000-02-04 | 2001-08-09 | Advanced Medicine, Inc. | Glycopeptide derivatives having antibiotic activity |
| JP4870314B2 (ja) * | 2000-05-02 | 2012-02-08 | セラヴァンス, インコーポレーテッド | シクロデキストリンを含むグリコペプチド抗生物質組成物 |
| AU2001259298A1 (en) | 2000-05-02 | 2001-11-12 | Advanced Medicine, Inc. | Polyacid glycopeptide derivatives |
| ATE402951T1 (de) | 2000-05-02 | 2008-08-15 | Theravance Inc | Verfahren zur reduktiven alkylierung von glykopeptiden |
| US6872804B2 (en) | 2000-06-22 | 2005-03-29 | Theravance, Inc. | Glycopeptide disulfide and thioester derivatives |
| WO2001098329A1 (en) * | 2000-06-22 | 2001-12-27 | Theravance, Inc. | Polyhydroxy glycopeptide derivatives |
| ES2302733T3 (es) * | 2000-06-22 | 2008-08-01 | Theravance, Inc. | Derivados carboxi-sacaridos de glucopeptido. |
| UA75083C2 (uk) * | 2000-06-22 | 2006-03-15 | Тераванс, Інк. | Похідні глікопептидфосфонатів |
| US6905669B2 (en) * | 2001-04-24 | 2005-06-14 | Supergen, Inc. | Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase |
| TWI312785B (en) * | 2001-08-24 | 2009-08-01 | Theravance Inc | Process for preparing vancomycin derivatives |
| TWI275594B (en) | 2001-08-24 | 2007-03-11 | Theravance Inc | Process for preparing vancomycin phosphonate derivatives |
| ATE322975T1 (de) | 2001-09-19 | 2006-04-15 | Procter & Gamble | Farbbedruckte mehrschichtstruktur, ein damit hergestellter absorbierender artikel und verfahren zu deren herstellung |
| TWI335332B (en) | 2001-10-12 | 2011-01-01 | Theravance Inc | Cross-linked vancomycin-cephalosporin antibiotics |
| CN101404986B (zh) | 2002-05-17 | 2011-09-28 | 赛奎拉公司 | 用于诊断和治疗感染性疾病的组合物和制药方法 |
| US20040033986A1 (en) * | 2002-05-17 | 2004-02-19 | Protopopova Marina Nikolaevna | Anti tubercular drug: compositions and methods |
| JP4347799B2 (ja) * | 2002-05-24 | 2009-10-21 | セラヴァンス, インコーポレーテッド | 架橋グリコペプチド−セファロスポリン抗生物質 |
| US6951963B2 (en) | 2002-06-17 | 2005-10-04 | Theravance, Inc. | Process for preparing N-protected β-amino aldehyde compounds |
| AU2003248896B2 (en) * | 2002-07-09 | 2010-04-22 | Fasgen, Llc | Methods of treating microbial infections in humans and animals |
| PT1565201T (pt) * | 2002-11-18 | 2019-02-05 | Vicuron Pharmaceuticals Llc | Métodos de administração de dalbavancina para o tratamento de infeções bacterianas |
| US20060074014A1 (en) * | 2002-11-18 | 2006-04-06 | Vicuron Pharmaceuticals Inc. | Dalbavancin compositions for treatment of bacterial infections |
| JP2007500222A (ja) * | 2003-05-23 | 2007-01-11 | セラヴァンス インコーポレーテッド | 架橋グリコペプチド−セファロスポリン抗生物質 |
| ATE388153T1 (de) * | 2003-07-11 | 2008-03-15 | Theravance Inc | Quervernetzte glycopeptid-cephalosporin- antibiotika |
| DE102004055582A1 (de) | 2004-11-18 | 2006-05-24 | Bayer Cropscience Ag | N-Heterocyclyl-phthalsäurediamide |
| JP4330169B2 (ja) | 2004-11-29 | 2009-09-16 | 国立大学法人名古屋大学 | グリコペプチド抗生物質モノマー誘導体 |
| US8304597B2 (en) | 2004-12-15 | 2012-11-06 | The Procter And Gamble Company | Method of using an absorbent article having a functional enhancement indicator |
| US7368422B2 (en) * | 2005-02-28 | 2008-05-06 | Novartis Vaccines And Diagnostics Inc. | Semi-synthetic rearranged vancomycin/desmethyl-vancomycin-based glycopeptides with antibiotic activity |
| US20070185015A1 (en) * | 2005-02-28 | 2007-08-09 | Chiron Corporation and North China Pharmaceutical Corporation | Semi-synthetic desmethyl-vancomycin-based glycopeptides with antibiotic activity |
| US7632918B2 (en) * | 2005-02-28 | 2009-12-15 | Novartis Vaccines And Diagnostics, Inc. | Semi-synthetic glycopeptides with antibiotic activity |
| CA2623198C (en) | 2005-09-22 | 2014-08-05 | Medivas, Llc | Bis-(a-amino)-diol-diester-containing poly(ester amide) and poly(ester urethane) compositions and methods of use |
| WO2007038246A2 (en) | 2005-09-22 | 2007-04-05 | Medivas, Llc | Solid polymer delivery compositions and methods for use thereof |
| WO2007084507A2 (en) * | 2006-01-13 | 2007-07-26 | The Scripps Research Institute | [ψ[CH2NH]PG4] GLYCOPEPTIDE ANTIBIOTIC ANALOGS |
| TW200808818A (en) * | 2006-05-26 | 2008-02-16 | Shionogi & Co | Glycopeptide antibiotic derivatives |
| RU2481354C2 (ru) | 2007-12-26 | 2013-05-10 | Шионоги Энд Ко., Лтд. | Гликозилированные гликопептидные антибиотические производные |
| EP2238102A4 (en) * | 2007-12-26 | 2011-03-09 | Lead Therapeutics Inc | NEW HALF-SYNTHETIC GLYCOPEPTIDES AS ANTIBACTERIAL AGENTS |
| US8841440B2 (en) | 2008-04-01 | 2014-09-23 | Cornell University | Organo-soluble chitosan salts and chitosan-derived biomaterials prepared thereof |
| GB2465863A (en) * | 2008-12-05 | 2010-06-09 | Lead Therapeutics Inc | Semi-synthetic heptapeptidic glycopeptides for the treatment of bacterial infections |
| CN101928330B (zh) * | 2009-06-26 | 2013-10-16 | 上海来益生物药物研究开发中心有限责任公司 | 一种新的化合物及其应用 |
| CA2868343A1 (en) * | 2011-03-24 | 2012-09-27 | Seachaid Pharmaceuticals, Inc. | Vancomycin derivatives |
| KR102237887B1 (ko) | 2013-03-15 | 2021-04-07 | 멜린타 서브시디어리 코프. | 항생제를 사용하여 과체중 및 비만 환자에서 감염을 치료하는 방법 |
| IN2013CH04314A (da) * | 2013-09-23 | 2015-08-28 | Jawaharlal Nehru Ct For Advanced Scient Res Jncasr | |
| EP3240574A1 (en) * | 2014-12-25 | 2017-11-08 | Jawaharlal Nehru Centre For Advanced Scientific Research | Glycopeptides and uses thereof |
| AU2017207875A1 (en) * | 2016-01-15 | 2018-08-09 | Universität Hamburg | Methods for the production of rhamnosylated flavonoids |
| US10689407B2 (en) * | 2016-01-28 | 2020-06-23 | Envista | Photo-cleavable primer compositions and methods of use |
| CN107325159A (zh) * | 2016-04-29 | 2017-11-07 | 中国科学院上海药物研究所 | 一类万古霉素衍生物、其制备方法、药物组合物和用途 |
| EP3634464A4 (en) * | 2017-05-22 | 2021-04-07 | Insmed Incorporated | COMPOUNDS DERIVED FROM GLYCOPEPTIDES AND THEIR USES |
| CN107987131B (zh) * | 2017-11-16 | 2021-03-09 | 上海来益生物药物研究开发中心有限责任公司 | 一组具有抗耐药性细菌活性的化合物、其制备方法和应用 |
| CN108409837B (zh) | 2018-03-06 | 2021-09-24 | 上海来益生物药物研究开发中心有限责任公司 | 一组具有抗耐药性细菌活性的糖肽类化合物、其制备方法和应用 |
| NL2023883B1 (en) * | 2019-09-24 | 2021-04-26 | Univ Leiden | Antibiotic compounds |
| CN111620931B (zh) * | 2020-06-12 | 2021-12-17 | 苏州博源医疗科技有限公司 | 万古霉素衍生物及其制备方法和应用 |
| CN114213284B (zh) * | 2022-01-04 | 2023-08-01 | 丽珠集团福州福兴医药有限公司 | (9h-芴-9-基)-癸基(2-氧代乙基)氨基甲酸甲酯及其合成方法 |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4497802A (en) | 1983-10-21 | 1985-02-05 | Eli Lilly And Company | N-Acyl glycopeptide derivatives |
| GB8428619D0 (en) | 1984-11-13 | 1984-12-19 | Lepetit Spa | Derivatives of antibiotic l 17046 |
| US4914187A (en) | 1984-11-13 | 1990-04-03 | Gruppo Lepetit S.P.A | Ester derivatives of antibiotic L 17046 |
| US4698327A (en) | 1985-04-25 | 1987-10-06 | Eli Lilly And Company | Novel glycopeptide derivatives |
| US4639433A (en) | 1985-08-14 | 1987-01-27 | Eli Lilly And Company | Glycopeptide derivatives |
| US4643987A (en) | 1985-08-14 | 1987-02-17 | Eli Lilly And Company | Modified glycopeptides |
| GB8704847D0 (en) * | 1987-03-02 | 1987-04-08 | Lepetit Spa | Substituted alkylamides of teicoplanin compounds |
| FR2632185B1 (fr) * | 1988-06-01 | 1992-05-22 | Rhone Poulenc Chimie | Silice pour compositions dentifrices compatible notamment avec le zinc |
| GB8817397D0 (en) * | 1988-07-21 | 1988-08-24 | Lepetit Spa | N15-alkyl & n15 n15-di-alkyl derivatives of teicoplanin antibiotics carrying functional groups on alkyl side chain |
| US5534420A (en) | 1988-07-28 | 1996-07-09 | Eli Lilly And Company | Biotransformation of glycopeptide antibiotics |
| ES2083374T3 (es) * | 1988-12-27 | 1996-04-16 | Lepetit Spa | Derivados amidicos en posicion c63 de 34-des(acetilglucosaminil)-34-desoxi-teicoplaninas. |
| IE64155B1 (en) | 1989-03-29 | 1995-07-12 | Lepetit Spa | New substituted alkylamide derivatives of teicoplanin |
| IL96603A (en) | 1989-12-13 | 1998-02-08 | Lilly Co Eli | Antibacterial glycopeptide derivatives, process for their preparation and pharmaceutical compositions containing them |
| AU647122B2 (en) | 1990-05-28 | 1994-03-17 | Gruppo Lepetit S.P.A. | C63-amide derivatives of 34-de(acetylglucosaminyl)-34-deoxy- teicoplanin and their use as medicaments against bacteria resistant to glycopeptide antibiotics |
| WO1992017456A1 (fr) | 1991-03-26 | 1992-10-15 | Fujisawa Pharmaceutical Co., Ltd. | Derive d'acide amine et sel dudit derive |
| US5750509A (en) | 1991-07-29 | 1998-05-12 | Gruppo Lepetit S.P.A. | Amide derivatives of antibiotic A 40926 |
| DE69203724T2 (de) * | 1991-07-29 | 1996-01-18 | Gruppo Lepetit S.P.A., Lainate | Amidderivate vom Antibiotikum A 40926. |
| US5840684A (en) | 1994-01-28 | 1998-11-24 | Eli Lilly And Company | Glycopeptide antibiotic derivatives |
| PE40996A1 (es) | 1994-01-28 | 1996-10-14 | Lilly Co Eli | Derivado de antibiotico de glucopeptido |
| IT1282586B1 (it) | 1996-02-08 | 1998-03-31 | Chemical And Biolog Ind | Composizioni farmaceutiche per il trattamento biologico delle infezioni dovute a ceppi di enterococcus faecium resistenti agli |
| CA2249323A1 (en) | 1996-03-21 | 1997-09-25 | Transcell Technologies, Inc. | Solid phase lipoglycopeptide library, compositions and methods |
| AU2441697A (en) | 1996-04-12 | 1997-11-07 | Eli Lilly And Company | Covalently-linked glycopeptide dimers |
| AU2609297A (en) | 1996-04-12 | 1997-11-07 | Eli Lilly And Company | Glycopeptide compounds |
| EP0912604B1 (en) | 1996-04-23 | 2001-11-14 | Biosearch Italia S.p.A. | Improved chemical process for preparing amide derivatives of antibiotic A 40926 |
| US5919756A (en) * | 1996-06-28 | 1999-07-06 | Eli Lilly And Company | Amides |
| US5952466A (en) | 1997-11-12 | 1999-09-14 | Eli Lilly And Company | Reductive alkylation of glycopeptide antibiotics |
| US5939382A (en) | 1996-11-21 | 1999-08-17 | Eli Lilly And Company | Reducing agent for reductive alkylation of glycopeptide antibiotics |
| US5916873A (en) | 1997-04-17 | 1999-06-29 | Eli Lilly And Company | Teicoplanin derivatives |
| US5952310A (en) | 1997-05-20 | 1999-09-14 | Eli Lilly And Company | Glycopeptide hexapeptides |
| US5977063A (en) | 1997-05-20 | 1999-11-02 | Eli Lilly And Company | Alkylated hexapeptides |
| US5919771A (en) | 1997-05-20 | 1999-07-06 | Eli Lilly And Company | Urea and thiourea derivatives of glycopeptides |
| US6518242B1 (en) * | 1998-02-20 | 2003-02-11 | Theravance, Inc. | Derivatives of glycopeptide antibacterial agents |
| EP1060189A1 (en) | 1998-02-20 | 2000-12-20 | Advanced Medicine, Inc. | Derivatives of glycopeptide antibacterial agents |
| DK1073447T3 (da) | 1998-05-01 | 2007-09-03 | Lilly Co Eli | N1-modificerede glycopeptider |
| CA2337103A1 (en) | 1998-07-14 | 2000-01-27 | Robert Kerns | Glycopeptide antibiotics, combinatorial libraries of glycopeptide antibiotics and methods of producing same |
| ES2201825T3 (es) | 1998-12-23 | 2004-03-16 | Theravance, Inc. | Derivados del glicopeptidos y composiciones farmaceuticas que los contienen. |
| UA75083C2 (uk) * | 2000-06-22 | 2006-03-15 | Тераванс, Інк. | Похідні глікопептидфосфонатів |
| JP4347799B2 (ja) * | 2002-05-24 | 2009-10-21 | セラヴァンス, インコーポレーテッド | 架橋グリコペプチド−セファロスポリン抗生物質 |
| ATE388153T1 (de) * | 2003-07-11 | 2008-03-15 | Theravance Inc | Quervernetzte glycopeptid-cephalosporin- antibiotika |
-
1999
- 1999-12-22 ES ES99965331T patent/ES2201825T3/es not_active Expired - Lifetime
- 1999-12-22 CZ CZ20010022A patent/CZ301184B6/cs not_active IP Right Cessation
- 1999-12-22 US US09/470,209 patent/US6392012B1/en not_active Expired - Lifetime
- 1999-12-22 DE DE69908819T patent/DE69908819T2/de not_active Expired - Lifetime
- 1999-12-22 AU AU31273/00A patent/AU768204B2/en not_active Expired
- 1999-12-22 BR BRPI9914221A patent/BRPI9914221B8/pt not_active IP Right Cessation
- 1999-12-22 WO PCT/US1999/030543 patent/WO2000039156A1/en not_active Ceased
- 1999-12-22 CN CNB99809434XA patent/CN1249081C/zh not_active Expired - Lifetime
- 1999-12-22 HK HK02102171.5A patent/HK1040721B/en unknown
- 1999-12-22 AT AT99965331T patent/ATE242783T1/de active
- 1999-12-22 SI SI9930389T patent/SI1140993T1/xx unknown
- 1999-12-22 JP JP2000591067A patent/JP4362017B2/ja not_active Expired - Fee Related
- 1999-12-22 HU HU0400887A patent/HU230190B1/hu unknown
- 1999-12-22 EP EP99965331A patent/EP1140993B1/en not_active Expired - Lifetime
- 1999-12-22 NZ NZ508594A patent/NZ508594A/en not_active IP Right Cessation
- 1999-12-22 PT PT99965331T patent/PT1140993E/pt unknown
- 1999-12-22 CA CA2336445A patent/CA2336445C/en not_active Expired - Lifetime
- 1999-12-22 IL IL14009399A patent/IL140093A0/xx active IP Right Grant
- 1999-12-22 KR KR1020017003918A patent/KR100665204B1/ko not_active Expired - Lifetime
- 1999-12-22 DK DK99965331T patent/DK1140993T3/da active
- 1999-12-22 PL PL348451A patent/PL198311B1/pl unknown
-
2000
- 2000-09-06 US US09/656,473 patent/US6444786B1/en not_active Expired - Lifetime
- 2000-11-01 US US09/674,456 patent/US6455669B1/en not_active Expired - Lifetime
- 2000-12-05 IL IL140093A patent/IL140093A/en not_active IP Right Cessation
- 2000-12-06 ZA ZA200007222A patent/ZA200007222B/xx unknown
- 2000-12-12 NO NO20006323A patent/NO326066B1/no not_active IP Right Cessation
-
2002
- 2002-03-06 US US10/092,088 patent/US6962970B2/en not_active Expired - Lifetime
-
2004
- 2004-04-15 US US10/825,038 patent/US6949681B2/en not_active Expired - Lifetime
-
2005
- 2005-05-13 US US11/128,901 patent/US7101964B2/en not_active Expired - Lifetime
-
2006
- 2006-04-17 US US11/405,234 patent/US7351791B2/en not_active Expired - Fee Related
-
2007
- 2007-10-24 US US11/977,377 patent/US7723470B2/en not_active Expired - Fee Related
-
2009
- 2009-05-08 US US12/437,778 patent/US8030445B2/en not_active Expired - Fee Related
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