IL208691A - Ctla4 molecule for use in preventing rheumatoid arthritis development in patients with early onset non-differentiated arthritis - Google Patents
Ctla4 molecule for use in preventing rheumatoid arthritis development in patients with early onset non-differentiated arthritisInfo
- Publication number
- IL208691A IL208691A IL208691A IL20869110A IL208691A IL 208691 A IL208691 A IL 208691A IL 208691 A IL208691 A IL 208691A IL 20869110 A IL20869110 A IL 20869110A IL 208691 A IL208691 A IL 208691A
- Authority
- IL
- Israel
- Prior art keywords
- arthritis
- gtg
- subjects
- development
- preventing
- Prior art date
Links
- 206010003246 arthritis Diseases 0.000 title 1
- 206010039073 rheumatoid arthritis Diseases 0.000 title 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102000043321 human CTLA4 Human genes 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5033608P | 2008-05-05 | 2008-05-05 | |
| US12/387,359 US7915222B2 (en) | 2008-05-05 | 2009-05-01 | Method of preventing the development of rheumatoid arthritis in subjects with undifferentiated arthritis |
| PCT/US2009/042761 WO2009137424A1 (en) | 2008-05-05 | 2009-05-05 | Method of preventing the development of rheumatoid arthritis in subjects with undifferentiated arthritis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL208691A0 IL208691A0 (en) | 2010-12-30 |
| IL208691A true IL208691A (en) | 2015-01-29 |
Family
ID=41264941
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL208691A IL208691A (en) | 2008-05-05 | 2010-10-13 | Ctla4 molecule for use in preventing rheumatoid arthritis development in patients with early onset non-differentiated arthritis |
Country Status (25)
| Country | Link |
|---|---|
| US (3) | US7915222B2 (enExample) |
| EP (2) | EP2279206B1 (enExample) |
| JP (1) | JP2011522795A (enExample) |
| KR (1) | KR20110014180A (enExample) |
| CN (1) | CN102037010A (enExample) |
| AR (1) | AR071672A1 (enExample) |
| AU (1) | AU2009244448B2 (enExample) |
| BR (1) | BRPI0912249A2 (enExample) |
| CA (1) | CA2723698C (enExample) |
| CL (1) | CL2009001082A1 (enExample) |
| DK (1) | DK2279206T3 (enExample) |
| EA (1) | EA201001749A1 (enExample) |
| ES (1) | ES2539840T3 (enExample) |
| HK (1) | HK1208230A1 (enExample) |
| HR (1) | HRP20150552T1 (enExample) |
| HU (1) | HUE025256T2 (enExample) |
| IL (1) | IL208691A (enExample) |
| MX (1) | MX2010011503A (enExample) |
| NZ (1) | NZ589020A (enExample) |
| PL (1) | PL2279206T3 (enExample) |
| PT (1) | PT2279206E (enExample) |
| SI (1) | SI2279206T1 (enExample) |
| TW (2) | TW201444575A (enExample) |
| WO (1) | WO2009137424A1 (enExample) |
| ZA (1) | ZA201007914B (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040022787A1 (en) | 2000-07-03 | 2004-02-05 | Robert Cohen | Methods for treating an autoimmune disease using a soluble CTLA4 molecule and a DMARD or NSAID |
| US7915222B2 (en) | 2008-05-05 | 2011-03-29 | Bristol-Myers Squibb Company | Method of preventing the development of rheumatoid arthritis in subjects with undifferentiated arthritis |
| RU2014117510A (ru) * | 2011-10-10 | 2015-11-20 | Медиммьюн Лимитед | Лечение ревматоидного артрита |
| US20140006055A1 (en) * | 2012-06-27 | 2014-01-02 | Iagnosis, Inc. | Integrated Medical Evaluation and Record Keeping System |
| EP2914292A4 (en) * | 2012-10-30 | 2016-05-04 | Univ Emory | Stimulation of bone formation by inhibition of CD28-co-stimulation |
| WO2014151230A2 (en) * | 2013-03-15 | 2014-09-25 | Bristol-Myers Squibb Company | Method of treating granulomatosis with polyangiitis |
| KR20160145789A (ko) * | 2014-04-25 | 2016-12-20 | 브리스톨-마이어스 스큅 컴퍼니 | 초기 ra를 갖는 대상체에서의 무약물 완화를 달성하기 위한 ctla4 화합물의 용도 |
| EP3283508B1 (en) | 2015-04-17 | 2021-03-17 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins with tunable affinities |
| KR102813968B1 (ko) | 2017-10-10 | 2025-05-29 | 알파인 이뮨 사이언시즈, 인코포레이티드 | Ctla-4 변이체 면역조절 단백질 및 이의 용도 |
| EP3735417A1 (en) | 2018-01-03 | 2020-11-11 | Alpine Immune Sciences, Inc. | Multi-domain immunomodulatory proteins and methods of use thereof |
| CN110148465B (zh) * | 2019-05-10 | 2023-07-04 | 中山大学孙逸仙纪念医院 | 一种用于分析类风湿性关节炎的系统 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5580756A (en) | 1990-03-26 | 1996-12-03 | Bristol-Myers Squibb Co. | B7Ig fusion protein |
| US7070776B1 (en) | 1990-03-26 | 2006-07-04 | Bristol-Myers Squibb Company | Methods for blocking binding of CD28 receptor to B7 |
| DK0606217T4 (da) | 1991-06-27 | 2009-03-30 | Bristol Myers Squibb Co | CTL4-receptor, fusionsproteiner indeholdende den samt anvendelse deraf |
| US6090914A (en) | 1991-06-27 | 2000-07-18 | Bristol-Myers Squibb Company | CTLA4/CD28Ig hybrid fusion proteins and uses thereof |
| US5770197A (en) | 1991-06-27 | 1998-06-23 | Bristol-Myers Squibb Company | Methods for regulating the immune response using B7 binding molecules and IL4-binding molecules |
| US5844095A (en) | 1991-06-27 | 1998-12-01 | Bristol-Myers Squibb Company | CTLA4 Ig fusion proteins |
| US5851795A (en) | 1991-06-27 | 1998-12-22 | Bristol-Myers Squibb Company | Soluble CTLA4 molecules and uses thereof |
| BR9405664A (pt) * | 1993-01-21 | 1996-04-30 | Univ Georgia | Composto imunogenio processos para evitar a toxicose por festuca em um herbivoro para tratar a toxicose por festuca em um herbivoro anticorpo purificado lingagem de célula de hidridoma e anticorpo |
| US5773253A (en) | 1993-01-22 | 1998-06-30 | Bristol-Myers Squibb Company | MYPPPY variants of CTL A4 and uses thereof |
| US6750334B1 (en) * | 1996-02-02 | 2004-06-15 | Repligen Corporation | CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor |
| JP4751493B2 (ja) | 1996-03-20 | 2011-08-17 | ブリストル−マイヤーズ スクイッブ カンパニー | Gp39/cd40およびctla4/cd28/b7経路のブロックによって免疫反応を阻止する方法およびそれに使用する組成物 |
| ZA98533B (en) | 1997-01-31 | 1999-07-22 | Bristol Myers Squibb Co | Soluble CTLA4 mutant molecules and uses thereof. |
| US20030219863A1 (en) | 1997-01-31 | 2003-11-27 | Bristol-Myers Squibb Company | Soluble CTLA4 mutant molecules and uses thereof |
| US7094874B2 (en) | 2000-05-26 | 2006-08-22 | Bristol-Myers Squibb Co. | Soluble CTLA4 mutant molecules |
| IL152316A0 (en) | 2000-06-09 | 2003-05-29 | Bristol Myers Squibb Co | Pharmaceutical compositions and kits for treating transplant rejection |
| US20040022787A1 (en) | 2000-07-03 | 2004-02-05 | Robert Cohen | Methods for treating an autoimmune disease using a soluble CTLA4 molecule and a DMARD or NSAID |
| CA2413190C (en) | 2000-07-03 | 2009-04-07 | Bristol-Myers Squibb Company | Methods for treating rheumatic diseases using a soluble ctla4 molecule |
| HUP0303930A3 (en) | 2001-01-26 | 2012-09-28 | Univ Emory | Methods of inducing organ transplant tolerance and correcting hemoglobinopathies |
| ATE390931T1 (de) | 2001-05-23 | 2008-04-15 | Bristol Myers Squibb Co | Verfahren zum schützen eines allogenen inseltransplantats mit löslichen ctla4- mutationsmolekülen |
| KR101088223B1 (ko) | 2002-12-23 | 2011-11-30 | 브리스톨-마이어스 스큅 컴퍼니 | 단백질 생산을 위한 포유류 세포 배양 방법에서의 생산물품질 향상 |
| BR0317723A (pt) | 2002-12-23 | 2005-11-22 | Bristol Myers Squibb Co | Processo de cultura de células de mamìfero para a produção de proteìna |
| EP1670499A4 (en) | 2003-08-04 | 2009-07-22 | Bristol Myers Squibb Co | METHODS OF TREATING A CARDIOVASCULAR DISEASE USING A SOLUBLE CTLA4 MOLECULE |
| US10092429B2 (en) * | 2005-08-22 | 2018-10-09 | Incept, Llc | Flared stents and apparatus and methods for delivering them |
| WO2007000020A1 (en) | 2005-06-29 | 2007-01-04 | Compumedics Limited | Sensor assembly with conductive bridge |
| CA2634547C (en) | 2005-12-20 | 2016-10-11 | Bristol-Myers Squibb Company | Stable ctla4 formulation for subcutaneous administration |
| TWI423986B (zh) | 2005-12-20 | 2014-01-21 | 必治妥美雅史谷比公司 | 組合物及製造組合物之方法 |
| US7528111B2 (en) | 2006-05-12 | 2009-05-05 | Bristol-Myers Squibb Company | Method of vaccinating subjects receiving immune modulating therapy |
| US7915222B2 (en) * | 2008-05-05 | 2011-03-29 | Bristol-Myers Squibb Company | Method of preventing the development of rheumatoid arthritis in subjects with undifferentiated arthritis |
-
2009
- 2009-05-01 US US12/387,359 patent/US7915222B2/en active Active
- 2009-05-05 AR ARP090101621A patent/AR071672A1/es unknown
- 2009-05-05 PT PT97434104T patent/PT2279206E/pt unknown
- 2009-05-05 PL PL09743410T patent/PL2279206T3/pl unknown
- 2009-05-05 HU HUE09743410A patent/HUE025256T2/en unknown
- 2009-05-05 NZ NZ589020A patent/NZ589020A/en not_active IP Right Cessation
- 2009-05-05 KR KR1020107027221A patent/KR20110014180A/ko not_active Ceased
- 2009-05-05 EA EA201001749A patent/EA201001749A1/ru unknown
- 2009-05-05 ES ES09743410.4T patent/ES2539840T3/es active Active
- 2009-05-05 DK DK09743410.4T patent/DK2279206T3/en active
- 2009-05-05 TW TW103129409A patent/TW201444575A/zh unknown
- 2009-05-05 BR BRPI0912249A patent/BRPI0912249A2/pt not_active Application Discontinuation
- 2009-05-05 AU AU2009244448A patent/AU2009244448B2/en not_active Ceased
- 2009-05-05 MX MX2010011503A patent/MX2010011503A/es active IP Right Grant
- 2009-05-05 CL CL2009001082A patent/CL2009001082A1/es unknown
- 2009-05-05 JP JP2011508582A patent/JP2011522795A/ja active Pending
- 2009-05-05 CN CN2009801162049A patent/CN102037010A/zh active Pending
- 2009-05-05 SI SI200931228T patent/SI2279206T1/sl unknown
- 2009-05-05 EP EP20090743410 patent/EP2279206B1/en active Active
- 2009-05-05 TW TW098114831A patent/TWI454278B/zh not_active IP Right Cessation
- 2009-05-05 EP EP15152246.3A patent/EP2891665A1/en not_active Withdrawn
- 2009-05-05 CA CA2723698A patent/CA2723698C/en active Active
- 2009-05-05 WO PCT/US2009/042761 patent/WO2009137424A1/en not_active Ceased
- 2009-05-05 HR HRP20150552TT patent/HRP20150552T1/hr unknown
-
2010
- 2010-10-13 IL IL208691A patent/IL208691A/en not_active IP Right Cessation
- 2010-11-04 ZA ZA2010/07914A patent/ZA201007914B/en unknown
-
2011
- 2011-02-10 US US13/024,601 patent/US8435952B2/en active Active
- 2011-03-07 HK HK15108768.6A patent/HK1208230A1/en unknown
-
2013
- 2013-03-27 US US13/851,166 patent/US9012408B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| IL208691A (en) | Ctla4 molecule for use in preventing rheumatoid arthritis development in patients with early onset non-differentiated arthritis | |
| WO2010088408A3 (en) | Subunit selective nmda receptor antagonists for the treatment of neurological conditions | |
| WO2008096271A3 (en) | Neuroprotection in demyelinating diseases | |
| EP2311963A3 (en) | Methods for increasing the resistance of plants to hypoxic conditions | |
| EP2266623A3 (en) | Prodrugs containing novel bio-cleavable linkers | |
| WO2005000201A3 (en) | Modulation of apolipoprotein (a) expression | |
| WO2005019418A3 (en) | Modulation of diacylglycerol acyltransferase 2 expression | |
| WO2008096127A3 (en) | Bicyclo[2.2.1]hept-7-ylamine derivatives and their use as m3 muscarinic receptor modulators | |
| WO2007138110A3 (en) | Compounds that interact with ion channels, in particular with ion channels from the kv family | |
| WO2001058869A3 (en) | Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators in treating respiratory and non-respiratory diseases | |
| MY140693A (en) | [1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia | |
| NZ598743A (en) | Substituted dihydro benzocycloalkyloxymethyl oxazolopyrimidinones, preparation and use thereof | |
| ZA201002115B (en) | Substituted n-phenyl-bipyrrolidine carboxamides and therapeutic use thereof | |
| WO2004048534A3 (en) | Modulation of cytokine-inducible kinase expression | |
| EP2208765A4 (en) | POLYURETHANE FOR A PRINTING INK BONDING AGENT, METHOD FOR THE PRODUCTION AND PRINTING INTE | |
| MX2010004094A (es) | Carboxamidas n-fenil-bipirrolidina sustituidas y su uso terapeutico. | |
| EP1671998A3 (en) | Process to form compound with indolocarbazole moieties | |
| WO2009143178A3 (en) | Pde10 inhibitors and related compositions and methods | |
| WO2005089504A3 (en) | Methods for the treatment of synucleinopathies | |
| WO2010077068A3 (en) | Benzoarylureido compounds, and composition for prevention or treatment of neurodegenerative brain disease containing the same | |
| WO2005118609A3 (en) | Small molecule stimulators of neuronal growth | |
| ATE523571T1 (de) | Tintensatz, aufzeichnungsverfahren und aufzeichnungsvorrichtung | |
| WO2007109288A3 (en) | Enantiomerically pure r-etifoxine, pharmaceutical compositions thereof and methods of their use | |
| AU2002353286A1 (en) | 3,6-disubstituted azabicyclo (3.1.0) hexane derivatives as muscarinic receptor antagonists | |
| WO2005089515A3 (en) | Methods for the treatment of synucleinopathies |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |