CA2652346A1 - Methods of regulating expression of genes or of gene products using substituted tetracycline compounds - Google Patents
Methods of regulating expression of genes or of gene products using substituted tetracycline compounds Download PDFInfo
- Publication number
- CA2652346A1 CA2652346A1 CA002652346A CA2652346A CA2652346A1 CA 2652346 A1 CA2652346 A1 CA 2652346A1 CA 002652346 A CA002652346 A CA 002652346A CA 2652346 A CA2652346 A CA 2652346A CA 2652346 A1 CA2652346 A1 CA 2652346A1
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- Prior art keywords
- doxycycline
- cell
- expression
- gene
- substituted tetracycline
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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| US80066206P | 2006-05-15 | 2006-05-15 | |
| US60/800,662 | 2006-05-15 | ||
| PCT/US2007/011699 WO2007133797A2 (en) | 2006-05-15 | 2007-05-15 | Methods of regulating expression of genes or of gene products using substituted tetracycline compounds |
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Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6756365B2 (en) * | 1991-11-06 | 2004-06-29 | Trustees Of Tufts College | Reducing tetracycline resistance in living cells |
| CA2318580A1 (en) * | 1998-01-23 | 1999-07-29 | Mark L. Nelson | Pharmaceutically active compounds and methods of use thereof |
| US20040224927A1 (en) | 2000-06-16 | 2004-11-11 | Trustees Of Tufts College | 7-N-substituted phenyl tetracycline compounds |
| US20020132798A1 (en) * | 2000-06-16 | 2002-09-19 | Nelson Mark L. | 7-phenyl-substituted tetracycline compounds |
| CN1450989A (zh) * | 2000-07-07 | 2003-10-22 | 塔夫茨大学信托人 | 7－取代的四环素化合物 |
| US7094806B2 (en) * | 2000-07-07 | 2006-08-22 | Trustees Of Tufts College | 7, 8 and 9-substituted tetracycline compounds |
| US8088820B2 (en) * | 2001-04-24 | 2012-01-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
| CA2531728A1 (en) | 2003-07-09 | 2005-02-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| US20060287283A1 (en) * | 2003-07-09 | 2006-12-21 | Paratek Pharmaceuticals, Inc. | Prodrugs of 9-aminomethyl tetracycline compounds |
| EP2269985A3 (en) * | 2004-10-25 | 2011-09-21 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| WO2006084265A1 (en) | 2005-02-04 | 2006-08-10 | Paratek Pharmaceuticals, Inc. | 11a, 12-DERIVATIVES OF TETRACYCLINE COMPOUNDS |
| JP2009502809A (ja) * | 2005-07-21 | 2009-01-29 | パラテック ファーマシューティカルズ インコーポレイテッド | １０−置換テトラサイクリンおよびその使用方法 |
| AU2007249695A1 (en) * | 2006-05-15 | 2007-11-22 | Paratek Pharmaceuticals, Inc. | Methods of regulating expression of genes or of gene products using substituted tetracycline compounds |
| PT2120963T (pt) | 2006-12-21 | 2018-12-17 | Paratek Pharm Innc | Compostos tetraciclina substituídos para tratamento de distúrbios inflamatórios da pele |
| PL2109602T3 (pl) * | 2006-12-21 | 2014-09-30 | Paratek Pharm Innc | Pochodne tetracyliny do leczenia zakażeń bakteryjnych, wirusowych i pasożytniczych |
| JP2010523684A (ja) | 2007-04-12 | 2010-07-15 | パラテック ファーマシューティカルズ インコーポレイテッド | テトラサイクリン化合物を用いる、脊髄筋委縮症を治療するための方法 |
| US20080283080A1 (en) * | 2007-05-15 | 2008-11-20 | Masood Habibi | Hair styling device |
| CA2717703A1 (en) | 2008-03-05 | 2009-09-11 | Paratek Pharmaceuticals, Inc. | Minocycline compounds and methods of use thereof |
| JP2011517697A (ja) * | 2008-04-14 | 2011-06-16 | パラテック ファーマシューティカルズ インコーポレイテッド | 置換テトラサイクリン化合物 |
| CA2730377C (en) | 2008-07-11 | 2017-09-19 | Neumedics | Tetracycline derivatives with reduced antibiotic activity and neuroprotective benefits |
| US8629334B2 (en) * | 2008-07-16 | 2014-01-14 | University Of Florida Research Foundation, Inc. | Viral-based transient-expression vector system for trees |
| PT2323972E (pt) | 2008-08-08 | 2013-10-09 | Tetraphase Pharmaceuticals Inc | Compostos de tetraciclina substituídos com c7-flúor |
| EP2341771A4 (en) * | 2008-09-19 | 2012-08-15 | Paratek Pharm Innc | TETRACYCLINE COMPOUNDS FOR THE TREATMENT OF RHEUMATOID ARTHRITIS AND RELATED THERAPEUTIC METHODS |
| EP2352833B1 (en) | 2008-10-01 | 2013-03-06 | TET Systems GmbH & Co. KG | Tetracycline inducible transcription control sequence |
| US8257956B2 (en) | 2008-10-28 | 2012-09-04 | E. I. Du Pont De Nemours And Company | Sulfonylurea-responsive repressor proteins |
| EP2427425B1 (en) | 2009-05-08 | 2017-03-08 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| IN2012DN02502A (https=) | 2009-08-28 | 2015-08-28 | Tetraphase Pharmaceuticals Inc | |
| WO2012071549A2 (en) | 2010-11-24 | 2012-05-31 | Clontech Laboratories, Inc. | Inducible expression system transcription modulators comprising a distributed protein transduction domain and methods for using the same |
| EP2710130B1 (en) | 2011-05-19 | 2022-06-29 | Fundación Pública Andaluza Progreso Y Salud | Highly inducible dual-promoter lentiviral tet-on system |
| BR112015004523B1 (pt) | 2012-08-31 | 2020-08-04 | Tetraphase Pharmaceuticals, Inc | Compostos de tetraciclina, composições farmacêuticas e seus usos |
| CN110582486B (zh) | 2016-10-19 | 2024-01-12 | 四相制药公司 | 艾若威四环素的结晶形式 |
| BR112019008897A2 (pt) | 2016-11-01 | 2019-08-13 | Paratek Pharm Innc | método para tratar pneumonia bacteriana adquirida na comunidade. |
| PT117254B (pt) | 2021-05-26 | 2024-04-18 | Hovione Farm S A | Método de síntese de compostos 9-aminometil tetraciclinas |
| CN118159660A (zh) * | 2021-10-18 | 2024-06-07 | 瑞泽恩制药公司 | 多核苷酸的受控转录 |
| TW202323529A (zh) | 2021-10-18 | 2023-06-16 | 美商再生元醫藥公司 | 包括腺病毒相關病毒聚核苷酸的真核細胞 |
Family Cites Families (119)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2990331A (en) * | 1956-11-23 | 1961-06-27 | Pfizer & Co C | Stable solutions of salts of tetracyclines for parenteral administration |
| US2980584A (en) * | 1957-10-29 | 1961-04-18 | Pfizer & Co C | Parenteral magnesium oxytetracycline acetic or lactic acid carboxamide vehicle preparation |
| US3062717A (en) * | 1958-12-11 | 1962-11-06 | Pfizer & Co C | Intramuscular calcium tetracycline acetic or lactic acid carboxamide vehicle preparation |
| US3862225A (en) | 1961-08-18 | 1975-01-21 | Pfizer | D-ring substituted tetracyclines |
| US3165531A (en) * | 1962-03-08 | 1965-01-12 | Pfizer & Co C | 13-substituted-6-deoxytetracyclines and process utilizing the same |
| US3454697A (en) * | 1965-06-08 | 1969-07-08 | American Cyanamid Co | Tetracycline antibiotic compositions for oral use |
| NL6607516A (https=) * | 1966-05-31 | 1967-12-01 | ||
| US4066694A (en) | 1971-02-09 | 1978-01-03 | Pfizer Inc. | 4-hydroxy-4-dedimethylamino-tetracyclines |
| US3622627A (en) | 1967-09-13 | 1971-11-23 | Pfizer | 4-dedimethylaminatetracycline and 5a, 6-anhydro derivatives thereof |
| DE1767891C3 (de) * | 1968-06-28 | 1980-10-30 | Pfizer | Verfahren zur Herstellung von wäßrigen arzneilichen Lösungen für die parenterale, perorale und lokale Anwendung mit einem Gehalt an einem Tetracyclinderivat |
| US3957980A (en) * | 1972-10-26 | 1976-05-18 | Pfizer Inc. | Doxycycline parenteral compositions |
| DE2442829A1 (de) * | 1974-09-06 | 1976-03-18 | Merck Patent Gmbh | Tetracyclische verbindungen und verfahren zu ihrer herstellung |
| US4018889A (en) * | 1976-01-02 | 1977-04-19 | Pfizer Inc. | Oxytetracycline compositions |
| US4126680A (en) * | 1977-04-27 | 1978-11-21 | Pfizer Inc. | Tetracycline antibiotic compositions |
| US4806529A (en) * | 1982-11-18 | 1989-02-21 | Trustees Of Tufts College, Tufts University | Tetracycline activity enhancement |
| US5589470A (en) * | 1990-02-26 | 1996-12-31 | Trustees Of Tufts College | Reducing tetracycline resistance in living cells |
| US5064821A (en) * | 1982-11-18 | 1991-11-12 | Trustees Of Tufts College | Method and compositions for overcoming tetracycline resistance within living cells |
| US4870009A (en) | 1982-11-22 | 1989-09-26 | The Salk Institute For Biological Studies | Method of obtaining gene product through the generation of transgenic animals |
| WO1985004662A1 (en) | 1984-04-13 | 1985-10-24 | Litton Bionetics, Inc. | Leukoregulin, an antitumor lymphokine, and its therapeutic uses |
| US4736866B1 (en) * | 1984-06-22 | 1988-04-12 | Transgenic non-human mammals | |
| US4806372A (en) * | 1985-02-15 | 1989-02-21 | Georgia Oil & Gas Co., Inc. | Nitrite-free-curing of bacon and product thereof |
| DE122007000007I2 (de) | 1986-04-09 | 2010-12-30 | Genzyme Corp | Genetisch transformierte Tiere, die ein gewünschtes Protein in Milch absondern |
| US5166320A (en) | 1987-04-22 | 1992-11-24 | University Of Connecticut | Carrier system and method for the introduction of genes into mammalian cells |
| US4873316A (en) | 1987-06-23 | 1989-10-10 | Biogen, Inc. | Isolation of exogenous recombinant proteins from the milk of transgenic mammals |
| EP0528810B1 (en) | 1991-03-22 | 1996-02-07 | CARSON, William S. | Container and pickup assembly for collection of recyclable materials |
| AU1970892A (en) | 1991-04-18 | 1992-11-17 | United States Of America, Represented By The Secretary, Department Of Health And Human Services, The | Identification of a new ehrlichia species from a patient suffering from ehrlichiosis |
| US5281628A (en) | 1991-10-04 | 1994-01-25 | American Cyanamid Company | 9-amino-7-(substituted)-6-demethyl-6-deoxytetracyclines |
| DE122006000058I1 (de) | 1991-10-04 | 2007-01-18 | Wyeth Corp | 7-Substituierte-9-substituierte Amino-6-Demethyl-6-Deoxy-Tetracycline |
| US5494903A (en) | 1991-10-04 | 1996-02-27 | American Cyanamid Company | 7-substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines |
| US6756365B2 (en) * | 1991-11-06 | 2004-06-29 | Trustees Of Tufts College | Reducing tetracycline resistance in living cells |
| US5442059A (en) | 1992-08-13 | 1995-08-15 | American Cyanamid Company | 9-[(substituted glycyl)amido)]-6-demethyl-6-deoxytetracyclines |
| US5328902A (en) | 1992-08-13 | 1994-07-12 | American Cyanamid Co. | 7-(substituted)-9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
| SG47520A1 (en) | 1992-08-13 | 1998-04-17 | American Cyanamid Co | New method for the production of 9-amino-6-demethyl-6-deoxytetracycline |
| US5420272A (en) | 1992-08-13 | 1995-05-30 | American Cyanamid Company | 7-(substituted)-8-(substituted)-9-](substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
| US5284963A (en) | 1992-08-13 | 1994-02-08 | American Cyanamid Company | Method of producing 7-(substituted)-9-[(substituted glycyl)-amidol]-6-demethyl-6-deoxytetra-cyclines |
| DE4227616C2 (de) | 1992-08-20 | 1995-04-13 | Sigma Tau Ind Farmaceuti | 17-(3-Furyl)-und 17-(4-Pyridazinyl)-5beta, 14beta-androstanderivate, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammemsetzungen |
| US5371076A (en) | 1993-04-02 | 1994-12-06 | American Cyanamid Company | 9-[(substituted glycyl)amido]-6-(substituted)-5-hydroxy-6-deoxytetracyclines |
| US5814618A (en) | 1993-06-14 | 1998-09-29 | Basf Aktiengesellschaft | Methods for regulating gene expression |
| US5912411A (en) * | 1993-06-14 | 1999-06-15 | University Of Heidelberg | Mice transgenic for a tetracycline-inducible transcriptional activator |
| US5464758A (en) | 1993-06-14 | 1995-11-07 | Gossen; Manfred | Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters |
| US5859310A (en) | 1993-06-14 | 1999-01-12 | Basf Aktiengesellschaft | Mice transgenic for a tetracycline-controlled transcriptional activator |
| US5654168A (en) | 1994-07-01 | 1997-08-05 | Basf Aktiengesellschaft | Tetracycline-inducible transcriptional activator and tetracycline-regulated transcription units |
| US5888981A (en) | 1993-06-14 | 1999-03-30 | Basf Aktiengesellschaft | Methods for regulating gene expression |
| US20030022315A1 (en) * | 1993-06-14 | 2003-01-30 | Basf Aktiengesellschaft And Knoll Aktiengesellschaft | Tetracycline-inducible transcriptional inhibitor fusion proteins |
| US6004941A (en) | 1993-06-14 | 1999-12-21 | Basf Aktiengesellschaft | Methods for regulating gene expression |
| US5866755A (en) * | 1993-06-14 | 1999-02-02 | Basf Aktiengellschaft | Animals transgenic for a tetracycline-regulated transcriptional inhibitor |
| JPH09500526A (ja) * | 1993-06-14 | 1997-01-21 | ベーアーエスエフ アクツィエンゲゼルシャフト | テトラサイクリン反応性プロモーターによる真核細胞の遺伝子発現の厳密な制御 |
| US5789156A (en) | 1993-06-14 | 1998-08-04 | Basf Ag | Tetracycline-regulated transcriptional inhibitors |
| ES2119038T3 (es) * | 1993-12-03 | 1998-10-01 | Uhrig Kanaltechnik Gmbh | Dispositivo para la estanqueidad de fugas internas de tubos y procedimiento de estanqueidad de fugas. |
| AU1279095A (en) | 1994-02-17 | 1995-09-04 | Pfizer Inc. | 9-(substituted amino)-alpha-6-deoxy-5-oxy tetracycline derivatives, their preparation and their use as antibiotics |
| US5530557A (en) | 1994-09-12 | 1996-06-25 | International Business Machines Corporation | Online placement of video files determined by a function of the bandwidth to space ratio of each of the storage devices in a server environment |
| WO1996034852A1 (en) | 1995-05-03 | 1996-11-07 | Pfizer, Inc. | Novel tetracycline derivatives |
| US5888891A (en) * | 1996-08-23 | 1999-03-30 | International Rectifier Corporation | Process for manufacturing a schottky diode with enhanced barrier height and high thermal stability |
| DE19640817A1 (de) * | 1996-10-02 | 1998-05-14 | Hermann Prof Dr Bujard | Rekombinantes Herstellungsverfahren für ein vollständiges Malaria-Antigen gp190/MSP 1 |
| US6087166A (en) * | 1997-07-03 | 2000-07-11 | Basf Aktiengesellschaft | Transcriptional activators with graded transactivation potential |
| CA2318580A1 (en) | 1998-01-23 | 1999-07-29 | Mark L. Nelson | Pharmaceutically active compounds and methods of use thereof |
| US6506740B1 (en) | 1998-11-18 | 2003-01-14 | Robert A. Ashley | 4-dedimethylaminotetracycline derivatives |
| ATE336238T1 (de) | 1998-11-18 | 2006-09-15 | Collagenex Pharm Inc | Neue 4-dedimethylaminotetracyclinderivate |
| JP4836375B2 (ja) * | 1999-06-07 | 2011-12-14 | ティーイーティー システムズ ホールディング ゲーエムベーハー ウント ツェーオー． カーゲー | 新規の、ｔｅｔリプレッサーに基づく転写調節タンパク質 |
| US6256365B1 (en) * | 1999-08-16 | 2001-07-03 | Analogic Corporation | Apparatus and method for reconstruction of images in a computed tomography system using oblique slices |
| US6500812B2 (en) * | 1999-09-14 | 2002-12-31 | Paratek Pharmaceuticals, Inc. | 13-substituted methacycline compounds |
| US6849615B2 (en) * | 1999-09-14 | 2005-02-01 | Paratek Pharmaceuticals, Inc. | 13-substituted methacycline compounds |
| EP2327687A3 (en) * | 1999-09-14 | 2012-08-15 | Trustees Of Tufts College | Methods of preparing substituted tetracyclines with transition metal-based chemistries |
| AU3105801A (en) * | 2000-01-24 | 2001-07-31 | Trustees Of Tufts College | Tetracycline compounds for treatment of cryptosporidium parvum related disorders |
| MXPA02009482A (es) * | 2000-03-31 | 2004-05-14 | Tufts College | Compuestos tetraciclinas sustituidos con grupos 7- y 9- carbamato, urea, tiourea, tiocarbamato y heteroaril-amino. |
| WO2001078479A2 (en) * | 2000-04-05 | 2001-10-18 | Einux, Inc. | Cooling system and method for high density electronics enclosure |
| WO2001087824A2 (en) * | 2000-05-15 | 2001-11-22 | Paratek Pharmaceuticals, Inc. | 7-substituted fused ring tetracycline compounds |
| WO2001098259A1 (en) | 2000-06-16 | 2001-12-27 | Trustees Of Tufts College | 7-phenyl-substituted tetracycline compounds |
| US20020132798A1 (en) * | 2000-06-16 | 2002-09-19 | Nelson Mark L. | 7-phenyl-substituted tetracycline compounds |
| US20040224927A1 (en) * | 2000-06-16 | 2004-11-11 | Trustees Of Tufts College | 7-N-substituted phenyl tetracycline compounds |
| US20020128238A1 (en) | 2000-06-16 | 2002-09-12 | Nelson Mark L. | 7-phenyl-substituted tetracycline compounds |
| AU2000257445A1 (en) | 2000-06-16 | 2002-01-02 | Trustees Of Tufts College | 7-n-substituted phenyl tetracycline compounds |
| US7094806B2 (en) * | 2000-07-07 | 2006-08-22 | Trustees Of Tufts College | 7, 8 and 9-substituted tetracycline compounds |
| US20050143353A1 (en) * | 2000-07-07 | 2005-06-30 | Paratek Pharmaceuticals, Inc. | 13-Substituted methacycline compounds |
| CN1450989A (zh) | 2000-07-07 | 2003-10-22 | 塔夫茨大学信托人 | 7－取代的四环素化合物 |
| EA013908B1 (ru) * | 2000-07-07 | 2010-08-30 | Трастис Оф Тафтс Коллидж | Замещенные соединения миноциклина (варианты), фармацевтическая композиция и способ лечения чувствительного к тетрациклину состояния млекопитающего |
| JP4963771B2 (ja) | 2000-07-07 | 2012-06-27 | トラスティーズ・オブ・タフツ・カレッジ | ７、８および９−置換テトラサイクリン化合物 |
| AU2000265203A1 (en) | 2000-08-04 | 2002-02-18 | Trustees Of Tufts College | 8-substituted tetracycline compounds |
| JP3777301B2 (ja) * | 2000-12-04 | 2006-05-24 | 本田技研工業株式会社 | 車両用多気筒エンジン |
| US7553828B2 (en) * | 2001-03-13 | 2009-06-30 | Paratek Pharmaceuticals, Inc. | 9-aminomethyl substituted minocycline compounds |
| EP1241160A1 (en) * | 2001-03-13 | 2002-09-18 | Glaxo Group Limited | Tetracycline derivatives and their use as antibiotic agents |
| WO2002072532A1 (en) * | 2001-03-13 | 2002-09-19 | Paratek Pharmaceuticals, Inc. | 7, 9-substituted tetracycline compounds |
| WO2002072506A2 (en) * | 2001-03-13 | 2002-09-19 | Paratek Pharmaceuticals, Inc. | 7-pyrollyl tetracycline compounds and methods of use thereof |
| JP2004530661A (ja) * | 2001-03-14 | 2004-10-07 | パラテック ファーマシューティカルズ インコーポレイテッド | 抗真菌剤としての置換テトラサイクリン化合物 |
| WO2002072031A2 (en) * | 2001-03-14 | 2002-09-19 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds as synergistic antifungal agents |
| US8088820B2 (en) * | 2001-04-24 | 2012-01-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
| US20060194773A1 (en) * | 2001-07-13 | 2006-08-31 | Paratek Pharmaceuticals, Inc. | Tetracyline compounds having target therapeutic activities |
| AU2002365120A1 (en) * | 2001-08-02 | 2003-07-15 | Paratek Pharmaceuticals, Inc. | Medicaments |
| WO2003023568A2 (en) * | 2001-09-10 | 2003-03-20 | Paratek Pharmaceuticals, Inc. | Computational method for determining oral bioavailability |
| DE10148195A1 (de) * | 2001-09-28 | 2003-04-24 | Rolf Gebhardt | Nicht-menschliches Tiermodell zur Untersuchung der Entstehung und der Therapie von Organfibrose |
| RU2300380C2 (ru) * | 2001-10-05 | 2007-06-10 | Тетрадженекс Фармасьютикалс, Инк. | Производные тетрациклина и способы их применения |
| EP2311799A1 (en) * | 2002-01-08 | 2011-04-20 | Paratek Pharmaceuticals, Inc. | 4-dedimethylamino tetracycline compounds |
| JP2005526754A (ja) * | 2002-03-08 | 2005-09-08 | パラテック ファーマシューティカルズ インコーポレイテッド | アミノメチル置換されたテトラサイクリン化合物 |
| KR101083498B1 (ko) * | 2002-03-21 | 2011-11-16 | 파라테크 파마슈티컬스, 인크. | 치환된 테트라시클린 화합물 |
| DK1532260T3 (da) * | 2002-08-28 | 2009-03-09 | Tet Systems Holding Gmbh & Co | Kromosomale lod til stringent regulering af genaktiviteter via transkriptionsaktiveringssystemer |
| US7437446B2 (en) | 2002-09-30 | 2008-10-14 | Electronic Data Systems Corporation | Reporting of abnormal computer resource utilization data |
| DE10249390A1 (de) * | 2002-10-23 | 2004-05-13 | Ruprecht-Karls-Universität Heidelberg | Rekombinante MVA-Stämme als potentielle Impfstoffe gegen P.falciparum-Malaria |
| CA2503446C (en) * | 2002-10-24 | 2012-12-18 | Paratek Pharmaceuticals, Inc. | Methods of using substituted tetracycline compounds to modulate rna |
| CA2531728A1 (en) | 2003-07-09 | 2005-02-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| US20060287283A1 (en) | 2003-07-09 | 2006-12-21 | Paratek Pharmaceuticals, Inc. | Prodrugs of 9-aminomethyl tetracycline compounds |
| US7739737B2 (en) * | 2003-07-29 | 2010-06-15 | Wisconsin Alumni Research Foundation | Method and apparatus to detect malicious software |
| US7672693B2 (en) | 2003-11-10 | 2010-03-02 | Nokia Corporation | Controlling method, secondary unit and radio terminal equipment |
| CA2553510C (en) * | 2004-01-15 | 2012-09-25 | Paratek Pharmaceuticals, Inc. | Aromatic a-ring derivatives of tetracycline compounds |
| AU2005299294B2 (en) | 2004-10-25 | 2012-06-07 | Paratek Pharmaceuticals, Inc. | 4-aminotetracyclines and methods of use thereof |
| EP2269985A3 (en) * | 2004-10-25 | 2011-09-21 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| JP5024784B2 (ja) | 2004-12-03 | 2012-09-12 | 独立行政法人科学技術振興機構 | 被検体生物の同定方法、この方法に使用する内部標準用ｄｎａ組成物及びその製造方法 |
| WO2006084265A1 (en) | 2005-02-04 | 2006-08-10 | Paratek Pharmaceuticals, Inc. | 11a, 12-DERIVATIVES OF TETRACYCLINE COMPOUNDS |
| DE102005011719A1 (de) | 2005-03-15 | 2006-09-28 | Clariant Produkte (Deutschland) Gmbh | Wasch- und Reinigungsmittel enthaltend Acetale als organische Lösemittel |
| JP2009502809A (ja) | 2005-07-21 | 2009-01-29 | パラテック ファーマシューティカルズ インコーポレイテッド | １０−置換テトラサイクリンおよびその使用方法 |
| EP2298324A1 (en) * | 2006-01-24 | 2011-03-23 | Paratek Pharmaceuticals, Inc. | Methods of increasing oral bioavailability of tetracyclines |
| TW200808812A (en) | 2006-04-12 | 2008-02-16 | Speedel Experimenta Ag | Imidazo compounds |
| AU2007249695A1 (en) * | 2006-05-15 | 2007-11-22 | Paratek Pharmaceuticals, Inc. | Methods of regulating expression of genes or of gene products using substituted tetracycline compounds |
| JP2010523684A (ja) * | 2007-04-12 | 2010-07-15 | パラテック ファーマシューティカルズ インコーポレイテッド | テトラサイクリン化合物を用いる、脊髄筋委縮症を治療するための方法 |
| JP2010525069A (ja) * | 2007-04-27 | 2010-07-22 | パラテック ファーマシューティカルズ インコーポレイテッド | アミノアルキルテトラサイクリン化合物の合成方法および精製方法 |
| BRPI0823405A2 (pt) * | 2007-07-06 | 2012-12-25 | Paratek Pharmaceuticals, Inc. | mÉtodos para sintetizar compostos de tetraciclina substituÍda |
| US7787981B2 (en) | 2008-05-16 | 2010-08-31 | Xerox Corporation | System for reliable collaborative assembly and maintenance of complex systems |
| KR101098447B1 (ko) | 2009-12-04 | 2011-12-26 | 매그나칩 반도체 유한회사 | 반도체 장치 |
| JP5706185B2 (ja) | 2011-02-22 | 2015-04-22 | 富士レビオ株式会社 | 測定装置及び測定方法 |
| US9713502B2 (en) | 2014-03-09 | 2017-07-25 | Gyrus Acmi, Inc. | Narrow band imaging with surgical loupes |
-
2007
- 2007-05-15 AU AU2007249695A patent/AU2007249695A1/en not_active Abandoned
- 2007-05-15 CA CA002652346A patent/CA2652346A1/en not_active Abandoned
- 2007-05-15 CA CA002652347A patent/CA2652347A1/en not_active Abandoned
- 2007-05-15 EP EP12171878.7A patent/EP2537934A3/en not_active Withdrawn
- 2007-05-15 US US11/803,854 patent/US20080118979A1/en not_active Abandoned
- 2007-05-15 EP EP10160144A patent/EP2218785A3/en not_active Withdrawn
- 2007-05-15 WO PCT/US2007/011699 patent/WO2007133797A2/en not_active Ceased
- 2007-05-15 EP EP11175509A patent/EP2431469A3/en not_active Withdrawn
- 2007-05-15 JP JP2009511045A patent/JP2009543544A/ja active Pending
- 2007-05-15 WO PCT/US2007/011700 patent/WO2007133798A2/en not_active Ceased
- 2007-05-15 JP JP2009511044A patent/JP2009537139A/ja active Pending
- 2007-05-15 EP EP07809091A patent/EP2026776A2/en not_active Withdrawn
- 2007-05-15 AU AU2007249696A patent/AU2007249696A1/en not_active Abandoned
- 2007-05-15 EP EP07777087A patent/EP2029749A2/en not_active Withdrawn
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2008
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2010
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2029749A2 (en) | 2009-03-04 |
| WO2007133798A3 (en) | 2009-07-09 |
| EP2026776A2 (en) | 2009-02-25 |
| WO2007133797A2 (en) | 2007-11-22 |
| EP2537934A2 (en) | 2012-12-26 |
| JP2009543544A (ja) | 2009-12-10 |
| EP2218785A3 (en) | 2010-12-29 |
| WO2007133798A2 (en) | 2007-11-22 |
| WO2007133797A3 (en) | 2008-03-20 |
| EP2431469A2 (en) | 2012-03-21 |
| JP2009537139A (ja) | 2009-10-29 |
| EP2431469A3 (en) | 2012-05-30 |
| AU2007249695A1 (en) | 2007-11-22 |
| US20090257985A1 (en) | 2009-10-15 |
| EP2218785A2 (en) | 2010-08-18 |
| CA2652347A1 (en) | 2007-11-22 |
| JP2010193904A (ja) | 2010-09-09 |
| AU2007249696A1 (en) | 2007-11-22 |
| US20080118979A1 (en) | 2008-05-22 |
| EP2537934A3 (en) | 2013-04-10 |
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