RU2012106150A - Вариантные формы уратоксидазы и их применение - Google Patents
Вариантные формы уратоксидазы и их применение Download PDFInfo
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- RU2012106150A RU2012106150A RU2012106150/10A RU2012106150A RU2012106150A RU 2012106150 A RU2012106150 A RU 2012106150A RU 2012106150/10 A RU2012106150/10 A RU 2012106150/10A RU 2012106150 A RU2012106150 A RU 2012106150A RU 2012106150 A RU2012106150 A RU 2012106150A
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- amino acid
- uricase
- pharmaceutical composition
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- 150000001413 amino acids Chemical class 0.000 claims abstract 24
- 108010092464 Urate Oxidase Proteins 0.000 claims abstract 23
- 235000001014 amino acid Nutrition 0.000 claims abstract 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 16
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract 10
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract 10
- 238000006467 substitution reaction Methods 0.000 claims abstract 10
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims abstract 8
- 239000004473 Threonine Substances 0.000 claims abstract 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract 4
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims abstract 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims abstract 4
- 229920000642 polymer Polymers 0.000 claims abstract 4
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims abstract 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims abstract 2
- 239000004471 Glycine Substances 0.000 claims abstract 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims abstract 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims abstract 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims abstract 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims abstract 2
- 239000004472 Lysine Substances 0.000 claims abstract 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims abstract 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims abstract 2
- 235000004279 alanine Nutrition 0.000 claims abstract 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims abstract 2
- 229930182817 methionine Natural products 0.000 claims abstract 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims abstract 2
- 238000004904 shortening Methods 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims 4
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims 2
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims 2
- 239000013060 biological fluid Substances 0.000 claims 2
- 239000008280 blood Substances 0.000 claims 2
- 210000004369 blood Anatomy 0.000 claims 2
- 210000001124 body fluid Anatomy 0.000 claims 2
- 239000010839 body fluid Substances 0.000 claims 2
- 229940116269 uric acid Drugs 0.000 claims 2
- 241000124008 Mammalia Species 0.000 abstract 3
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- C—CHEMISTRY; METALLURGY
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- 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
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
- C12N9/0044—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on other nitrogen compounds as donors (1.7)
- C12N9/0046—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on other nitrogen compounds as donors (1.7) with oxygen as acceptor (1.7.3)
- C12N9/0048—Uricase (1.7.3.3)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- 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
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- 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
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
- C12N9/0044—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on other nitrogen compounds as donors (1.7)
- C12N9/0046—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on other nitrogen compounds as donors (1.7) with oxygen as acceptor (1.7.3)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y107/00—Oxidoreductases acting on other nitrogenous compounds as donors (1.7)
- C12Y107/03—Oxidoreductases acting on other nitrogenous compounds as donors (1.7) with oxygen as acceptor (1.7.3)
- C12Y107/03003—Factor-independent urate hydroxylase (1.7.3.3), i.e. uricase
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- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Toxicology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
1. Фармацевтическая композиция, содержащая конъюгат уриказы, где уриказа конъюгирована с полимером, и уриказа выбрана из группы, состоящей из:(a) изолированной укороченной уриказы млекопитающего, которая укорочена с аминоконца на 6 аминокислот и дополнительно содержит аминокислотную замену на треонин в положении 46 (S46T), аминокислотную замену на треонин в положении 7 (D7T), аминокислотную замену на лизин в положении 291 (R291K) и аминокислотную замену на серин в положении 301 (T301S), где указанное укорочение и аминокислотная замена относятся к не укороченной уриказе свиньи, имеющей аминокислотную последовательность SEQ ID NO: 11;(b) изолированной укороченной уриказы млекопитающего из (a), дополнительно содержащей аминоконцевую аминокислоту, где аминоконцевой аминокислотой является аланин, глицин, пролин, серин или треонин;(с) изолированной укороченной уриказы млекопитающего из (b), в которой аминоконцевой аминокислотой является треонин;(d) изолированной укороченной уриказы млекопитающего из (a), состоящей из аминокислотной последовательности SEQ ID NO: 8;(e) белка изолированной укороченной уриказы млекопитающего из (d), дополнительно содержащего N-концевую аминокислоту, где N-концевой аминокислотой является метионин; и(f) изолированной укороченной уриказы млекопитающего из (е) состоящей из аминокислотной последовательности SEQ ID NO: 7.2. Фармацевтическая композиция по п.1, в которой полимер представляет собой полиэтиленгликоль.3. Фармацевтическая композиция по п.2, содержащая от 2 до 12 молекул полиэтиленгликоля на каждую субъединицу уриказы.4. Фармацевтическая композиция по п.3, содержащая от 3 до 10 молекул полиэтиленгликоля на каждую субъ�
Claims (14)
1. Фармацевтическая композиция, содержащая конъюгат уриказы, где уриказа конъюгирована с полимером, и уриказа выбрана из группы, состоящей из:
(a) изолированной укороченной уриказы млекопитающего, которая укорочена с аминоконца на 6 аминокислот и дополнительно содержит аминокислотную замену на треонин в положении 46 (S46T), аминокислотную замену на треонин в положении 7 (D7T), аминокислотную замену на лизин в положении 291 (R291K) и аминокислотную замену на серин в положении 301 (T301S), где указанное укорочение и аминокислотная замена относятся к не укороченной уриказе свиньи, имеющей аминокислотную последовательность SEQ ID NO: 11;
(b) изолированной укороченной уриказы млекопитающего из (a), дополнительно содержащей аминоконцевую аминокислоту, где аминоконцевой аминокислотой является аланин, глицин, пролин, серин или треонин;
(с) изолированной укороченной уриказы млекопитающего из (b), в которой аминоконцевой аминокислотой является треонин;
(d) изолированной укороченной уриказы млекопитающего из (a), состоящей из аминокислотной последовательности SEQ ID NO: 8;
(e) белка изолированной укороченной уриказы млекопитающего из (d), дополнительно содержащего N-концевую аминокислоту, где N-концевой аминокислотой является метионин; и
(f) изолированной укороченной уриказы млекопитающего из (е) состоящей из аминокислотной последовательности SEQ ID NO: 7.
2. Фармацевтическая композиция по п.1, в которой полимер представляет собой полиэтиленгликоль.
3. Фармацевтическая композиция по п.2, содержащая от 2 до 12 молекул полиэтиленгликоля на каждую субъединицу уриказы.
4. Фармацевтическая композиция по п.3, содержащая от 3 до 10 молекул полиэтиленгликоля на каждую субъединицу уриказы.
5. Фармацевтическая композиция по п.2, в которой каждая молекула полиэтиленгликоля имеет молекулярную массу от 1 кД до 100 кД.
6. Фармацевтическая композиция по п.5, в которой каждая молекула полиэтиленгликоля имеет молекулярную массу от 1 кД до 50 кД.
7. Фармацевтическая композиция по п.6, в которой каждая молекула полиэтиленгликоля имеет молекулярную массу от 5 кД до 20 кД.
8. Фармацевтическая композиция по п.7, в которой каждая молекула полиэтиленгликоля имеет молекулярную массу приблизительно 10 кД.
9. Фармацевтическая композиция по п.1, пригодная для повторного введения.
10. Фармацевтическая композиция по пп.2-8, пригодная для повторного введения.
11. Способ снижения уровней мочевой кислоты в биологической жидкости организма нуждающегося в этом пациента, включающий введение в организм пациента фармацевтической композиции по п.9.
12. Способ снижения уровней мочевой кислоты в биологической жидкости организма нуждающегося в этом пациента, включающий введение в организм пациента фармацевтической композиции по п.10.
13. Способ по п.11, где биологической жидкостью является кровь.
14. Способ по п.12, где биологической жидкостью является кровь.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67057305P | 2005-04-11 | 2005-04-11 | |
| US60/670,573 | 2005-04-11 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007141625/10A Division RU2451074C2 (ru) | 2005-04-11 | 2006-04-11 | Вариантные формы уратоксидазы и их применение |
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| RU2012106150A true RU2012106150A (ru) | 2013-08-27 |
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| RU2007141625/10A RU2451074C2 (ru) | 2005-04-11 | 2006-04-11 | Вариантные формы уратоксидазы и их применение |
| RU2012106148/10A RU2012106148A (ru) | 2005-04-11 | 2012-02-20 | Вариантные формы уратоксидазы и их применение |
| RU2012106116A RU2610680C9 (ru) | 2005-04-11 | 2012-02-20 | Вариантные формы уратоксидазы и их применение |
| RU2012106150/10A RU2012106150A (ru) | 2005-04-11 | 2012-02-20 | Вариантные формы уратоксидазы и их применение |
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| RU2007141625/10A RU2451074C2 (ru) | 2005-04-11 | 2006-04-11 | Вариантные формы уратоксидазы и их применение |
| RU2012106148/10A RU2012106148A (ru) | 2005-04-11 | 2012-02-20 | Вариантные формы уратоксидазы и их применение |
| RU2012106116A RU2610680C9 (ru) | 2005-04-11 | 2012-02-20 | Вариантные формы уратоксидазы и их применение |
Country Status (26)
| Country | Link |
|---|---|
| US (12) | US8188224B2 (ru) |
| EP (3) | EP2947145A1 (ru) |
| JP (6) | JP2008535500A (ru) |
| KR (1) | KR20080009111A (ru) |
| CN (1) | CN101198693B (ru) |
| AU (1) | AU2006235495B2 (ru) |
| BR (1) | BRPI0612941A2 (ru) |
| CA (1) | CA2604399A1 (ru) |
| CY (1) | CY1124138T1 (ru) |
| CZ (1) | CZ2007695A3 (ru) |
| DK (1) | DK3321359T3 (ru) |
| ES (2) | ES2856881T3 (ru) |
| FR (1) | FR15C0067I2 (ru) |
| HU (2) | HU229068B1 (ru) |
| IL (1) | IL186510A (ru) |
| LT (1) | LT3321359T (ru) |
| MX (1) | MX2007012547A (ru) |
| NZ (1) | NZ562292A (ru) |
| PL (2) | PL215285B1 (ru) |
| PT (1) | PT3321359T (ru) |
| RU (4) | RU2451074C2 (ru) |
| SG (1) | SG161247A1 (ru) |
| SI (1) | SI3321359T1 (ru) |
| TW (1) | TWI366467B (ru) |
| WO (1) | WO2006110819A2 (ru) |
| ZA (1) | ZA200708650B (ru) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2158923B1 (en) | 1998-08-06 | 2013-02-27 | Mountain View Pharmaceuticals, Inc. | Peg-urate oxidase conjugates and use thereof |
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