ZA988676B - Amino-terminally truncated MCP-2 as chemokine antagonists. - Google Patents
Amino-terminally truncated MCP-2 as chemokine antagonists.Info
- Publication number
- ZA988676B ZA988676B ZA9808676A ZA988676A ZA988676B ZA 988676 B ZA988676 B ZA 988676B ZA 9808676 A ZA9808676 A ZA 9808676A ZA 988676 A ZA988676 A ZA 988676A ZA 988676 B ZA988676 B ZA 988676B
- Authority
- ZA
- South Africa
- Prior art keywords
- amino
- terminally truncated
- chemokine antagonists
- truncated mcp
- mcp
- Prior art date
Links
Classifications
-
- 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
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4813—Exopeptidases (3.4.11. to 3.4.19)
-
- 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
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/521—Chemokines
- C07K14/523—Beta-chemokines, e.g. RANTES, I-309/TCA-3, MIP-1alpha, MIP-1beta/ACT-2/LD78/SCIF, MCP-1/MCAF, MCP-2, MCP-3, LDCF-1, LDCF-2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Cardiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- AIDS & HIV (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97116863A EP0906954A1 (de) | 1997-09-29 | 1997-09-29 | Aminoterminalen verkürzten C-C Chemokine als Chemokine Antagonist |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA988676B true ZA988676B (en) | 1999-12-03 |
Family
ID=8227408
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA9808675A ZA988675B (en) | 1997-09-29 | 1998-09-22 | Amino-terminally truncated rantes as chemokine antagonists. |
ZA9808676A ZA988676B (en) | 1997-09-29 | 1998-09-22 | Amino-terminally truncated MCP-2 as chemokine antagonists. |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA9808675A ZA988675B (en) | 1997-09-29 | 1998-09-22 | Amino-terminally truncated rantes as chemokine antagonists. |
Country Status (29)
Country | Link |
---|---|
US (5) | US6977071B2 (de) |
EP (6) | EP0906954A1 (de) |
JP (2) | JP4230659B2 (de) |
KR (2) | KR100542934B1 (de) |
CN (3) | CN1148447C (de) |
AR (2) | AR013529A1 (de) |
AT (3) | ATE263242T1 (de) |
AU (2) | AU750341B2 (de) |
BG (2) | BG64757B1 (de) |
BR (2) | BR9812565A (de) |
CA (2) | CA2305017A1 (de) |
CY (1) | CY1110927T1 (de) |
CZ (2) | CZ299478B6 (de) |
DE (3) | DE69823218T2 (de) |
DK (3) | DK1439231T3 (de) |
EA (2) | EA003942B1 (de) |
EE (2) | EE200000152A (de) |
ES (3) | ES2215324T3 (de) |
HK (3) | HK1032425A1 (de) |
HU (2) | HU226468B1 (de) |
IL (2) | IL135352A (de) |
NO (2) | NO20001584L (de) |
NZ (3) | NZ503234A (de) |
PL (2) | PL196427B1 (de) |
PT (3) | PT1019507E (de) |
SK (2) | SK286495B6 (de) |
UA (2) | UA73080C2 (de) |
WO (2) | WO1999016877A1 (de) |
ZA (2) | ZA988675B (de) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7067117B1 (en) | 1997-09-11 | 2006-06-27 | Cambridge University Technical Services, Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
US6989435B2 (en) | 1997-09-11 | 2006-01-24 | Cambridge University Technical Services Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
AU1616499A (en) * | 1997-12-01 | 1999-06-16 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Chemokine variants and methods of use |
US7238711B1 (en) | 1999-03-17 | 2007-07-03 | Cambridge University Technical Services Ltd. | Compounds and methods to inhibit or augment an inflammatory response |
AU1259501A (en) * | 1999-10-25 | 2001-05-08 | Euroscreen S.A. | Processed human chemokines phc-1 and phc-2 |
EP1167527A1 (de) * | 2000-06-22 | 2002-01-02 | Euroscreen S.A. | Prozessierte Menschliche Chemokine: PHC-1 und PHC-2 |
AU2505601A (en) * | 1999-11-15 | 2001-05-30 | Wolf-Georg Forssmann | Novel use of hcc-2 |
CA2316405A1 (en) * | 2000-05-26 | 2001-11-26 | Ian Clark-Lewis | Modulation of inflammation by protease products |
EP1176200A3 (de) | 2000-06-20 | 2005-01-12 | Switch Biotech Aktiengesellschaft | Verwendung von Polypeptiden oder diese kodierende Nukleinsäuren zur Diagnose oder Behandlung von Hauterkrankung oder Wundheilung sowie ihre Verwendung zur Indentifizierung von pharmakologisch aktiven Substanzen |
UA77950C2 (en) * | 2000-10-04 | 2007-02-15 | Applied Research Systems | Use of mutants of cc chemokines for treatment of multiple sclerosis |
GB2373785A (en) * | 2001-03-28 | 2002-10-02 | Rega Inst For Medical Res | Truncating chemokines using dipeptidyl peptidase IV |
ATE421974T1 (de) | 2001-12-17 | 2009-02-15 | Serono Lab | Chemokine mutanten, die als chemokine antagonisten wirken |
WO2004104216A2 (en) * | 2003-05-21 | 2004-12-02 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with dipeptidylpeptidase iv (dpp4) |
DE102005049637A1 (de) * | 2005-10-14 | 2007-04-26 | Rheinisch-Westfälische Technische Hochschule Aachen | Antagonisten gegen die Interaktion von PF4 und RANTES |
ES2453592T3 (es) | 2007-08-02 | 2014-04-08 | Novimmune Sa | Anticuerpos anti-RANTES y métodos de uso de los mismos |
US20130053257A1 (en) * | 2010-02-08 | 2013-02-28 | Paul E. Oran | RANTES Multiplexed Assay, RANTES Variants Related to Disease, and RANTES Variants Related to Enzymatice Activity |
CN102884194B (zh) | 2010-03-11 | 2015-07-22 | 健康研究股份有限公司 | 含增强免疫应答的Fc融合蛋白的方法和组合物 |
TW201718851A (zh) * | 2015-09-18 | 2017-06-01 | 通用醫院公司 | 具有抗化學排斥(anti-fugetactic)性質之經修飾自然殺手細胞及其用途 |
EP3813869B1 (de) | 2018-05-28 | 2023-10-18 | Université de Genève | Ccr5-inhibitor zur verwendung bei der behandlung einer neuroinflammatorischen erkrankung, die eine gehirnentzündung beinhaltet |
US11629196B2 (en) | 2020-04-27 | 2023-04-18 | Incelldx, Inc. | Method of treating SARS-CoV-2-associated hypercytokinemia by administering a human monoclonal antibody (PRO-140) that inhibits CCR5/CCL5 binding interactions |
US11402391B2 (en) | 2020-12-21 | 2022-08-02 | Incelldx, Inc. | Methods of treating a long-hauler subject for chronic COVID-19 by administering a CCR5 or CCL5 antagonist |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01265099A (ja) | 1987-10-08 | 1989-10-23 | Stichting Rega Vzw | 抗hiv活性をもつ3’,−フルオロプリン−2’,3’−ジデオキシリボシド類 |
US5739103A (en) * | 1993-11-12 | 1998-04-14 | Dana-Farber Cancer Institute | Chemokine N-terminal deletion mutations |
NZ296570A (en) * | 1994-12-08 | 1998-11-25 | Glaxo Group Ltd | Anti-inflammatory peptides related to rantes |
AU1532697A (en) * | 1996-01-12 | 1997-08-01 | Genetics Institute Inc. | Beta-chemokine, h1305 (mcp-2) |
EP0889961A2 (de) * | 1996-03-27 | 1999-01-13 | Icos Corporation | Monozyte chemotaktisches protein-5 stoffe und verfahren |
FR2748938B1 (fr) * | 1996-05-22 | 1998-07-31 | Pasteur Institut | Utilisation de molecules antagonistes de chemokines pour leur activite antivirale notamment contre un retrovirus de type vih |
US6168784B1 (en) * | 1997-09-03 | 2001-01-02 | Gryphon Sciences | N-terminal modifications of RANTES and methods of use |
-
1997
- 1997-09-29 EP EP97116863A patent/EP0906954A1/de not_active Withdrawn
- 1997-12-19 EP EP97122471A patent/EP0905240A1/de not_active Withdrawn
-
1998
- 1998-03-10 EP EP98104216A patent/EP0905241A1/de not_active Withdrawn
- 1998-09-22 ZA ZA9808675A patent/ZA988675B/xx unknown
- 1998-09-22 ZA ZA9808676A patent/ZA988676B/xx unknown
- 1998-09-28 CZ CZ20001146A patent/CZ299478B6/cs not_active IP Right Cessation
- 1998-09-28 KR KR1020007003020A patent/KR100542934B1/ko not_active IP Right Cessation
- 1998-09-28 BR BR9812565-6A patent/BR9812565A/pt not_active Application Discontinuation
- 1998-09-28 PT PT98951476T patent/PT1019507E/pt unknown
- 1998-09-28 WO PCT/EP1998/006143 patent/WO1999016877A1/en active IP Right Grant
- 1998-09-28 CN CNB988095726A patent/CN1148447C/zh not_active Expired - Fee Related
- 1998-09-28 EE EEP200000152A patent/EE200000152A/xx unknown
- 1998-09-28 AU AU97474/98A patent/AU750341B2/en not_active Ceased
- 1998-09-28 AR ARP980104820A patent/AR013529A1/es active IP Right Grant
- 1998-09-28 EP EP98951476A patent/EP1019507B1/de not_active Expired - Lifetime
- 1998-09-28 CN CNB031492991A patent/CN1233415C/zh not_active Expired - Fee Related
- 1998-09-28 AT AT98951476T patent/ATE263242T1/de active
- 1998-09-28 PL PL339545A patent/PL196427B1/pl not_active IP Right Cessation
- 1998-09-28 EA EA200000378A patent/EA003942B1/ru not_active IP Right Cessation
- 1998-09-28 NZ NZ503234A patent/NZ503234A/en unknown
- 1998-09-28 EA EA200000379A patent/EA003940B1/ru not_active IP Right Cessation
- 1998-09-28 SK SK451-2000A patent/SK286495B6/sk not_active IP Right Cessation
- 1998-09-28 CN CNB988095696A patent/CN1145693C/zh not_active Expired - Fee Related
- 1998-09-28 ES ES98947553T patent/ES2215324T3/es not_active Expired - Lifetime
- 1998-09-28 DK DK04007579T patent/DK1439231T3/da active
- 1998-09-28 AR ARP980104819A patent/AR013528A1/es active IP Right Grant
- 1998-09-28 NZ NZ516027A patent/NZ516027A/en unknown
- 1998-09-28 DE DE69823218T patent/DE69823218T2/de not_active Expired - Lifetime
- 1998-09-28 AU AU94420/98A patent/AU750606B2/en not_active Ceased
- 1998-09-28 EE EEP200000151A patent/EE200000151A/xx unknown
- 1998-09-28 NZ NZ503235A patent/NZ503235A/xx unknown
- 1998-09-28 JP JP2000513946A patent/JP4230659B2/ja not_active Expired - Fee Related
- 1998-09-28 HU HU0003563A patent/HU226468B1/hu not_active IP Right Cessation
- 1998-09-28 DE DE69838188T patent/DE69838188T2/de not_active Expired - Lifetime
- 1998-09-28 AT AT98947553T patent/ATE264390T1/de active
- 1998-09-28 EP EP98947553A patent/EP1021541B1/de not_active Expired - Lifetime
- 1998-09-28 JP JP2000513947A patent/JP4233214B2/ja not_active Expired - Fee Related
- 1998-09-28 WO PCT/EP1998/006142 patent/WO1999016876A1/en active IP Right Grant
- 1998-09-28 UA UA2000042496A patent/UA73080C2/uk unknown
- 1998-09-28 PT PT98947553T patent/PT1021541E/pt unknown
- 1998-09-28 PT PT04007579T patent/PT1439231E/pt unknown
- 1998-09-28 ES ES98951476T patent/ES2218860T3/es not_active Expired - Lifetime
- 1998-09-28 CA CA002305017A patent/CA2305017A1/en not_active Abandoned
- 1998-09-28 DK DK98947553T patent/DK1021541T3/da active
- 1998-09-28 AT AT04007579T patent/ATE368742T1/de active
- 1998-09-28 CA CA002304827A patent/CA2304827A1/en not_active Abandoned
- 1998-09-28 DK DK98951476T patent/DK1019507T3/da active
- 1998-09-28 CZ CZ20001147A patent/CZ299479B6/cs not_active IP Right Cessation
- 1998-09-28 PL PL339559A patent/PL197569B1/pl not_active IP Right Cessation
- 1998-09-28 KR KR1020007003019A patent/KR100560275B1/ko not_active IP Right Cessation
- 1998-09-28 EP EP04007579A patent/EP1439231B1/de not_active Expired - Lifetime
- 1998-09-28 UA UA2000042499A patent/UA73081C2/uk unknown
- 1998-09-28 ES ES04007579T patent/ES2287601T3/es not_active Expired - Lifetime
- 1998-09-28 DE DE69822856T patent/DE69822856T2/de not_active Expired - Lifetime
- 1998-09-28 SK SK450-2000A patent/SK286439B6/sk not_active IP Right Cessation
- 1998-09-28 HU HU0003505A patent/HU226414B1/hu not_active IP Right Cessation
- 1998-09-28 BR BR9812394-7A patent/BR9812394A/pt not_active Application Discontinuation
-
2000
- 2000-03-22 BG BG104267A patent/BG64757B1/bg unknown
- 2000-03-22 BG BG104266A patent/BG64679B1/bg unknown
- 2000-03-27 NO NO20001584A patent/NO20001584L/no not_active Application Discontinuation
- 2000-03-28 NO NO20001609A patent/NO20001609D0/no unknown
- 2000-03-28 US US09/537,858 patent/US6977071B2/en not_active Expired - Fee Related
- 2000-03-28 US US09/537,859 patent/US6905676B2/en not_active Expired - Fee Related
- 2000-03-29 IL IL135352A patent/IL135352A/en not_active IP Right Cessation
- 2000-03-29 IL IL135351A patent/IL135351A/en not_active IP Right Cessation
-
2001
- 2001-04-25 HK HK01102961A patent/HK1032425A1/xx not_active IP Right Cessation
- 2001-04-25 HK HK04105182A patent/HK1062637A1/xx not_active IP Right Cessation
- 2001-04-25 HK HK01102962A patent/HK1032426A1/xx not_active IP Right Cessation
-
2005
- 2005-03-07 US US11/072,454 patent/US7326411B2/en not_active Expired - Fee Related
- 2005-05-06 US US11/123,089 patent/US7338653B2/en not_active Expired - Fee Related
- 2005-05-18 US US11/131,221 patent/US20050220790A1/en not_active Abandoned
-
2007
- 2007-10-08 CY CY20071101290T patent/CY1110927T1/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ZA988676B (en) | Amino-terminally truncated MCP-2 as chemokine antagonists. | |
ZA977011B (en) | Muscarinic antagonists. | |
AU3633997A (en) | Chemokine receptor antagonists | |
EP0684823A4 (de) | Fibrinogenrezeptorantagonisten. | |
AU4251197A (en) | Therapeutic chemokine antagonists | |
ZA987055B (en) | Substituted 4-benzoylpyrazoles. | |
ZA973024B (en) | Ketoacid endothelin antagonists. | |
ZA987058B (en) | Substituted 4-benzoylpyrazoles. | |
ZA98387B (en) | Novel microorganisms. | |
MXPA01012165A (es) | Antagonistas ccr3 del receptor de quimiocina. | |
ZA9811502B (en) | Novel composition. | |
ZA97928B (en) | Novel heteroaryl-oxazolidinones. | |
ZA971184B (en) | Endothelin antagonists. | |
ZA988586B (en) | Truncated cellulase compositions. | |
ZA9710609B (en) | Cement composition. | |
ZA987B (en) | Substituted 4-benzoylpyrazoles. | |
DE69707656D1 (en) | Synthese von cycloalkyldiarylphosphin | |
ZA97576B (en) | Mammalian CX3C chemokine genes. | |
AU9384998A (en) | Cxc chemokine | |
IL135352A0 (en) | Truncated mcp-2 as chemokine antagonist | |
ZA975895B (en) | Ceramic compositions. | |
ZA969259B (en) | Skip. | |
ZA978504B (en) | Assay. | |
ZA983795B (en) | Substituted 4-benzoyl-pyrazoles. | |
IL127551A0 (en) | Chemokine beta-15 |