JP2012516897A - シュードモナス・エルギノーサ(PseudomonasAeruginosa)感染の治療のための抗生物質と抗体療法との組み合わせ - Google Patents
シュードモナス・エルギノーサ(PseudomonasAeruginosa)感染の治療のための抗生物質と抗体療法との組み合わせ Download PDFInfo
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| JP2013515079A (ja) | 2009-12-22 | 2013-05-02 | カロバイオス ファーマシューティカルズ インコーポレイティッド | 低レベルの病原性シュードモナス・エルギノーサ(Pseudomonasaeruginosa)感染症を有する患者のスタフィロコッカス(Staphylococcus)感染症を治療する方法 |
| KR102111171B1 (ko) | 2011-06-10 | 2020-05-14 | 메디뮨 엘엘씨 | 항슈도모나스 psl 결합 분자 및 그의 용도 |
| SMT202000542T1 (it) * | 2011-11-07 | 2020-11-10 | Medimmune Ltd | Terapie di combinazione utilizzando molecole di legame anti-psl e pcrv di pseudomonas |
| CN114072145B (zh) * | 2020-06-01 | 2024-06-11 | 北京三诺佳邑生物技术有限责任公司 | 特异性识别假单胞菌pcrv的抗体及其用途 |
| FR3114970B1 (fr) | 2020-10-08 | 2023-06-30 | Univ Tours | Combinaison d’anticorps inhalés avec des agents immunomodulateurs pour le traitement ou la prévention d’inféctions respiratoires |
| WO2024261584A1 (en) * | 2023-06-17 | 2024-12-26 | Abgenics Lifesciences Private Limited | A composition effective against beta-lactam antibiotic-resistant pseudomonas aeruginosa |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62187417A (ja) * | 1985-12-10 | 1987-08-15 | ジエネテイツク システムズ コ−ポレ−シヨン | 緑膿菌血清型に対する交さ反応性かつ交さ防御性単クロ−ン性抗体 |
| JPS63500035A (ja) * | 1985-06-06 | 1988-01-07 | ジエネテイツク システムズ コ−ポレイシヨン | プソイドモナス アエルギノサ 外毒素aに対する保護用ヒトモノクロ−ナル抗体 |
| JPS63102697A (ja) * | 1986-07-03 | 1988-05-07 | ジエネテイツク システムズ コ−ポレ−シヨン | シュ−ドモナスアエルギノ−ザ鞭毛に対するモノクロ−ナル抗体 |
| JP2005500250A (ja) * | 2001-01-26 | 2005-01-06 | エムシーダブリユー リサーチ フオンデーシヨン インコーポレーテツド | シュードモナスv抗原を用いる免疫化のための方法および組成物 |
| WO2008030988A2 (en) * | 2006-09-06 | 2008-03-13 | The Regents Of The University Of California | Selectively targeted antimicrobial peptides and the use thereof |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5132405A (en) | 1987-05-21 | 1992-07-21 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
| JPS6412935A (en) | 1987-07-02 | 1989-01-17 | Mitsubishi Electric Corp | Constant-speed travel device for vehicle |
| AU3580800A (en) | 1998-11-25 | 2000-06-26 | Mcw Research Foundation, Inc. | Method of and compositions for immunization with the (pseudomonas) v antigen |
| EP1761561B1 (en) | 2004-01-20 | 2015-08-26 | KaloBios Pharmaceuticals, Inc. | Antibody specificity transfer using minimal essential binding determinants |
| AU2005306502B2 (en) | 2004-11-16 | 2012-11-15 | Humanigen, Inc. | Immunoglobulin variable region cassette exchange |
| US8211648B2 (en) | 2005-07-22 | 2012-07-03 | Kalobios Pharmaceuticals, Inc. | Secretion of antibodies without signal peptides from bacteria |
| EA201000903A1 (ru) * | 2007-11-30 | 2011-02-28 | Калобиос Фармасьютикалс, Инк. | Антитела к pcrv-антигену pseudomonas aeruginosa |
-
2010
- 2010-02-04 CA CA2751433A patent/CA2751433A1/en not_active Abandoned
- 2010-02-04 US US12/700,599 patent/US20100272736A1/en not_active Abandoned
- 2010-02-04 EP EP10704049A patent/EP2393515A1/en not_active Withdrawn
- 2010-02-04 JP JP2011549261A patent/JP2012516897A/ja active Pending
- 2010-02-04 WO PCT/US2010/023214 patent/WO2010091189A1/en not_active Ceased
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63500035A (ja) * | 1985-06-06 | 1988-01-07 | ジエネテイツク システムズ コ−ポレイシヨン | プソイドモナス アエルギノサ 外毒素aに対する保護用ヒトモノクロ−ナル抗体 |
| JPS62187417A (ja) * | 1985-12-10 | 1987-08-15 | ジエネテイツク システムズ コ−ポレ−シヨン | 緑膿菌血清型に対する交さ反応性かつ交さ防御性単クロ−ン性抗体 |
| JPS63102697A (ja) * | 1986-07-03 | 1988-05-07 | ジエネテイツク システムズ コ−ポレ−シヨン | シュ−ドモナスアエルギノ−ザ鞭毛に対するモノクロ−ナル抗体 |
| JP2005500250A (ja) * | 2001-01-26 | 2005-01-06 | エムシーダブリユー リサーチ フオンデーシヨン インコーポレーテツド | シュードモナスv抗原を用いる免疫化のための方法および組成物 |
| WO2008030988A2 (en) * | 2006-09-06 | 2008-03-13 | The Regents Of The University Of California | Selectively targeted antimicrobial peptides and the use thereof |
Non-Patent Citations (8)
| Title |
|---|
| JPN5012007144; FAURE KARINE: 'EFFECTS OF MONOCLONAL ANTI-PCRV ANTIBODY ON PSEUDOMONAS AERUGINOSA-INDUCED 以下備考' JOURNAL OF IMMUNE BASED THERAPIES AND VACCINES V1 N1, 20030813, P2, BIOMED CENTRAL LTD. * |
| JPN5012007145; NEELY A N: 'PASSIVE ANTI-PCRV TREATMENT PROTECTS BURNED MICE AGAINST PSEUDOMONAS AERUGINOSA CHALLENGE' BURNS V31 N2, 20050301, P153-158, BUTTERWORTH HEINEMANN * |
| JPN5012007146; FRANK D W: 'GENERATION AND CHARACTERIZATION OF A PROTECTIVE MONOCLONAL ANTIBODY TO PSEUDOMONAS AERUGINOSA PCRV' JOURNAL OF INFECTIOUS DISEASES V186 N1, 20020701, P64-73, UNIVERSITY OF CHICAGO PRESS * |
| JPN5012007147; BAER MARK: 'AN ENGINEERED HUMAN ANTIBODY FAB FRAGMENT SPECIFIC FOR PSEUDOMONAS AERUGINOSA PCRV 以下備考' INFECTION AND IMMUNITY V77 N3, 20081222, P1083-1090 * |
| JPN5012007148; LYNCH S V: 'NOVEL STRATEGIES TO COMBAT BACTERIAL VIRULENCE' CURRENT OPINION IN CRITICAL CARE V14 N5, 200810, P593-599 * |
| JPN6015008426; 日本化学療法学会雑誌 Vol. 53,No. 8, 2005, p. 476-482 * |
| JPN6015008429; The Japanese Journal of Antibiotics Vol. 59,No. 1, 2006, p. 11-20 * |
| JPN6015008431; 感染症学雑誌 Vol. 82,No. 5, 2008, p. 466-470 * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2393515A1 (en) | 2011-12-14 |
| US20100272736A1 (en) | 2010-10-28 |
| CA2751433A1 (en) | 2010-08-12 |
| WO2010091189A1 (en) | 2010-08-12 |
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