UY37811A - Una composición inmunogénica que tiene estabilidad mejorada, inmunogeneicidad potenciada y reactogenicidad reducida y proceso para la preparación de la misma - Google Patents
Una composición inmunogénica que tiene estabilidad mejorada, inmunogeneicidad potenciada y reactogenicidad reducida y proceso para la preparación de la mismaInfo
- Publication number
- UY37811A UY37811A UY0001037811A UY37811A UY37811A UY 37811 A UY37811 A UY 37811A UY 0001037811 A UY0001037811 A UY 0001037811A UY 37811 A UY37811 A UY 37811A UY 37811 A UY37811 A UY 37811A
- Authority
- UY
- Uruguay
- Prior art keywords
- antigen
- immunogenic composition
- preparation
- same
- improved stability
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5252—Virus inactivated (killed)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/70—Multivalent vaccine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0016—Combination vaccines based on diphtheria-tetanus-pertussis
- A61K39/0018—Combination vaccines based on acellular diphtheria-tetanus-pertussis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/05—Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella, Corynebacterium; Propionibacterium
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/099—Bordetella
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/102—Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/125—Picornaviridae, e.g. calicivirus
- A61K39/13—Poliovirus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/29—Hepatitis virus
- A61K39/292—Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
-
- 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
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- 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
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/32011—Picornaviridae
- C12N2770/32611—Poliovirus
- C12N2770/32634—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN201721025513 | 2017-07-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UY37811A true UY37811A (es) | 2019-01-02 |
Family
ID=63556364
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UY0001037811A UY37811A (es) | 2017-07-18 | 2018-07-17 | Una composición inmunogénica que tiene estabilidad mejorada, inmunogeneicidad potenciada y reactogenicidad reducida y proceso para la preparación de la misma |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US11179453B2 (enExample) |
| EP (1) | EP3655024A1 (enExample) |
| JP (1) | JP7404226B2 (enExample) |
| KR (1) | KR102657910B1 (enExample) |
| CN (1) | CN111032078A (enExample) |
| AU (1) | AU2018302767B2 (enExample) |
| BR (1) | BR112020000999A2 (enExample) |
| CA (1) | CA3070039A1 (enExample) |
| CO (1) | CO2020001765A2 (enExample) |
| EA (1) | EA202090316A1 (enExample) |
| GE (1) | GEP20227386B (enExample) |
| JO (1) | JOP20180069B1 (enExample) |
| MX (1) | MX2020000441A (enExample) |
| PE (1) | PE20201443A1 (enExample) |
| PH (1) | PH12020500133A1 (enExample) |
| SG (1) | SG11202000224SA (enExample) |
| TW (1) | TWI786153B (enExample) |
| UA (1) | UA128204C2 (enExample) |
| UY (1) | UY37811A (enExample) |
| WO (1) | WO2019016654A1 (enExample) |
| ZA (1) | ZA202000889B (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101359953B1 (ko) * | 2005-06-27 | 2014-02-21 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 면역원성 조성물 |
| AU2007224734C1 (en) | 2006-03-10 | 2016-07-14 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Live attenuated Bordetella strains as a single dose vaccine against whooping cough |
| CN102448490B (zh) | 2009-04-28 | 2015-05-13 | 国家健康与医学研究院 | 用于预防或治疗过敏原引起的气道疾病的疫苗 |
| EP3697439A1 (en) * | 2017-10-18 | 2020-08-26 | Institut Pasteur de Lille | Bordetella strains expressing serotype 3 fimbriae |
| JOP20190242A1 (ar) | 2018-10-12 | 2020-04-12 | Serum Institute Of India Pvt Ltd | تركيبة لقاح توليفي تشمل فيروس شلل الأطفال ذو جرعة مخفّضة خاملة التنشيط وطريقة لتحضيرها |
| WO2020165920A1 (en) * | 2019-02-12 | 2020-08-20 | Biological E Limited | Multivalent vaccine composition |
| CN112138155B (zh) * | 2019-06-28 | 2022-04-12 | 怡道生物科技(苏州)有限公司 | 一种复合佐剂系统及制备该佐剂的方法 |
| JOP20200214A1 (ar) | 2019-09-03 | 2021-03-03 | Serum Institute Of India Pvt Ltd | تركيبات مولدة للمناعة ضد الأمراض المعوية وطرق لتحضيرها |
| EP3988290A1 (en) | 2020-10-23 | 2022-04-27 | Carl Zeiss Vision International GmbH | Method for manufacturing a spectacle lens |
| EP3988288A1 (en) | 2020-10-23 | 2022-04-27 | Carl Zeiss Vision International GmbH | Method of manufacturing a spectacle lens |
| EP3988289A1 (en) | 2020-10-23 | 2022-04-27 | Carl Zeiss Vision International GmbH | Method of manufacturing a spectacle lens |
| WO2022114921A1 (ko) * | 2020-11-30 | 2022-06-02 | 주식회사 엘지화학 | 알루미늄 부형제를 이용하여 다가 혼합백신 내 백일해 균 유래 엔도톡신 제거 방법 |
| MY208608A (en) * | 2021-04-20 | 2025-05-20 | Km Biologics Co Ltd | Liquid sextuple vaccine composition |
| CN120826235A (zh) * | 2023-03-16 | 2025-10-21 | 艾芬尼维克斯公司 | 免疫原性组合物 |
| CN119799602A (zh) * | 2025-03-17 | 2025-04-11 | 艾美坚持生物制药有限公司 | 一种破伤风梭状芽胞杆菌发酵培养基及培养方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE122010000016I1 (de) | 1992-05-23 | 2010-07-08 | Glaxosmithkline Biolog Sa | Kombinierte Impfstoffe, die Hepatitis-B-Oberflächen antigen und andere Antigene enthalten |
| EP0833662B2 (en) * | 1995-06-23 | 2011-01-26 | SmithKline Beecham Biologicals S.A. | A vaccine composition comprsing a Haemophilus influenzae B polysaccharide conjugate antigen adsorbed onto aluminium phosphate |
| BR9714980A (pt) | 1997-09-15 | 2001-11-06 | Pasteur Merieux Msd | Vacinas multivalentes |
| GB9806456D0 (en) | 1998-03-25 | 1998-05-27 | Smithkline Beecham Biolog | Vaccine composition |
| EP1004314A1 (fr) | 1998-11-26 | 2000-05-31 | Pasteur Merieux MSD | Vaccin T.d. Polio rappel pour une population vaccinée ou sensibilisée |
| UA79735C2 (uk) | 2000-08-10 | 2007-07-25 | Глаксосмітклайн Байолоджікалз С.А. | Очищення антигенів вірусу гепатиту b (hbv) для використання у вакцинах |
| GB0313916D0 (en) * | 2003-06-16 | 2003-07-23 | Glaxosmithkline Biolog Sa | Vaccine composition |
| GB0405787D0 (en) | 2004-03-15 | 2004-04-21 | Chiron Srl | Low dose vaccines |
| GB0616226D0 (en) * | 2006-08-15 | 2006-09-27 | Novartis Ag | Processes |
| CN103585624A (zh) | 2006-09-07 | 2014-02-19 | 葛兰素史密丝克莱恩生物有限公司 | 疫苗 |
| PE20100366A1 (es) * | 2008-10-24 | 2010-05-21 | Panacea Biotec Ltd | Novedosas composiciones de vacuna con tos ferina acelular asi como el metodo para su elaboracion |
| PE20100365A1 (es) * | 2008-10-24 | 2010-05-21 | Panacea Biotec Ltd | Novedosas vacunas de combinacion con tos ferina de celulas enteras y metodo para su elaboracion |
| EP3459562B1 (en) * | 2011-01-05 | 2024-03-20 | Bharat Biotech International Limited | A combination heptavalent vaccine |
| JP6564367B2 (ja) * | 2013-08-05 | 2019-08-21 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 併用免疫原性組成物 |
| BR112018005291A2 (pt) * | 2015-09-16 | 2018-10-09 | Lg Chemical Ltd | composição para vacina combinada para dosagem múltipla |
-
2018
- 2018-07-13 JP JP2020502265A patent/JP7404226B2/ja active Active
- 2018-07-13 CN CN201880048015.1A patent/CN111032078A/zh active Pending
- 2018-07-13 US US16/631,965 patent/US11179453B2/en active Active
- 2018-07-13 AU AU2018302767A patent/AU2018302767B2/en active Active
- 2018-07-13 CA CA3070039A patent/CA3070039A1/en active Pending
- 2018-07-13 UA UAA202000861A patent/UA128204C2/uk unknown
- 2018-07-13 SG SG11202000224SA patent/SG11202000224SA/en unknown
- 2018-07-13 EA EA202090316A patent/EA202090316A1/ru unknown
- 2018-07-13 MX MX2020000441A patent/MX2020000441A/es unknown
- 2018-07-13 BR BR112020000999-7A patent/BR112020000999A2/pt unknown
- 2018-07-13 WO PCT/IB2018/055180 patent/WO2019016654A1/en not_active Ceased
- 2018-07-13 GE GEAP201815276A patent/GEP20227386B/en unknown
- 2018-07-13 EP EP18768937.7A patent/EP3655024A1/en active Pending
- 2018-07-13 KR KR1020207004735A patent/KR102657910B1/ko active Active
- 2018-07-13 PE PE2020000084A patent/PE20201443A1/es unknown
- 2018-07-17 UY UY0001037811A patent/UY37811A/es not_active Application Discontinuation
- 2018-07-17 TW TW107124600A patent/TWI786153B/zh active
- 2018-07-17 JO JOP/2018/0069A patent/JOP20180069B1/ar active
-
2020
- 2020-01-17 PH PH12020500133A patent/PH12020500133A1/en unknown
- 2020-02-11 ZA ZA2020/00889A patent/ZA202000889B/en unknown
- 2020-02-17 CO CONC2020/0001765A patent/CO2020001765A2/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX2020000441A (es) | 2020-08-17 |
| KR102657910B1 (ko) | 2024-04-18 |
| US20200206331A1 (en) | 2020-07-02 |
| UA128204C2 (uk) | 2024-05-08 |
| JOP20180069A1 (ar) | 2019-01-18 |
| JP7404226B2 (ja) | 2023-12-25 |
| SG11202000224SA (en) | 2020-02-27 |
| PH12020500133A1 (en) | 2021-02-08 |
| PE20201443A1 (es) | 2020-12-10 |
| ZA202000889B (en) | 2021-06-30 |
| KR20200042470A (ko) | 2020-04-23 |
| TWI786153B (zh) | 2022-12-11 |
| TW201919690A (zh) | 2019-06-01 |
| CO2020001765A2 (es) | 2020-05-29 |
| JP2020527571A (ja) | 2020-09-10 |
| AU2018302767B2 (en) | 2025-04-10 |
| US11179453B2 (en) | 2021-11-23 |
| CN111032078A (zh) | 2020-04-17 |
| JOP20180069B1 (ar) | 2022-09-15 |
| GEP20227386B (en) | 2022-06-10 |
| EA202090316A1 (ru) | 2020-12-08 |
| WO2019016654A1 (en) | 2019-01-24 |
| CA3070039A1 (en) | 2019-01-24 |
| EP3655024A1 (en) | 2020-05-27 |
| BR112020000999A2 (pt) | 2020-07-14 |
| AU2018302767A1 (en) | 2020-03-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| UY37811A (es) | Una composición inmunogénica que tiene estabilidad mejorada, inmunogeneicidad potenciada y reactogenicidad reducida y proceso para la preparación de la misma | |
| CO2018005229A2 (es) | Vacuna de virus sincitial respiratorio | |
| BR112018002406A2 (pt) | anticorpos que neutralizam potentemente o vírus da hepatite b e usos dos mesmos | |
| AR092896A1 (es) | Composiciones inmunogenicas | |
| MX2018010586A (es) | Nanovacuna de activacion de "sting" para inmunoterapia. | |
| AR041880A1 (es) | Composicion inmunogena | |
| WO2015142671A3 (en) | Influenza virus vectors and uses therefor | |
| BR112018004242A2 (pt) | composições de vacina que possuem estabilidade e imunogenicidade aumentadas | |
| ZA202401922B (en) | Coronavirus vaccine formulations | |
| PE20100366A1 (es) | Novedosas composiciones de vacuna con tos ferina acelular asi como el metodo para su elaboracion | |
| MX2023006203A (es) | Vacunas novedosas contra el virus de zika. | |
| BRPI0607551A2 (pt) | vacinas de combinação de helicobacter e circovìrus porcino e métodos de uso | |
| MX2023011163A (es) | Formulaciones para vacuna contra coronavirus. | |
| PE20211648A1 (es) | Composicion de vacuna combinada que comprende dosis reducidas del virus inactivado de la polio y metodo de preparacion de la misma | |
| MX2024006589A (es) | Formulaciones de vacunas contra el coronavirus. | |
| BR112017004181A2 (pt) | ?gene, vetor, célula hospedeira, partículas similares a vírus, vacina para vírus de papiloma humano, composição imunogênica, adjuvante, método para o preparo de uma vacina de papiloma humano, proteína de capsídeo principal e proteína hpv l1? | |
| AR088907A1 (es) | Vacuna | |
| UY31569A1 (es) | Vacunas contra la malaria | |
| AU2017261706A1 (en) | Inactivating pathogens and producing highly immunogenic inactivated vaccines using a dual oxidation process | |
| PE20200004A1 (es) | Composicion de vacuna multivalente novedosa | |
| AR095425A1 (es) | Vacuna, uso y procedimiento para prevenir una infección por picornavirus | |
| WO2020012428A8 (en) | New vaccines against avian reoviruses | |
| AR101256A1 (es) | Composición vacunal que comprende ipv y ciclodextrinas | |
| AR117191A1 (es) | Composiciones inmunogénicas | |
| BR112018000037A2 (pt) | partículas semelhantes a vírus recombinantes usando a proteína gag do vírus da imunodeficiência bovina (vlp de bgag), vacina, vetor plasmidial de transferência para produzir a vlp de bgag, método para fazer a vlp de bgag, método para preparar a vacina |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RDES | Application refused |
Effective date: 20241206 |