JP2011522796A5 - - Google Patents
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- JP2011522796A5 JP2011522796A5 JP2011508615A JP2011508615A JP2011522796A5 JP 2011522796 A5 JP2011522796 A5 JP 2011522796A5 JP 2011508615 A JP2011508615 A JP 2011508615A JP 2011508615 A JP2011508615 A JP 2011508615A JP 2011522796 A5 JP2011522796 A5 JP 2011522796A5
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| US6187548B1 (en) | 1993-05-23 | 2001-02-13 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Methods using human calcium sensor protein, fragments thereof and DNA encoding same |
| US6239270B1 (en) | 1993-05-24 | 2001-05-29 | Rhone-Poulenc Rorer S.A. | Nucleic acids encoding human calcium sensor protein |
| EP0972198B2 (de) * | 1997-03-10 | 2013-12-11 | Roche Diagnostics GmbH | Verfahren zur simultanen bestimmung von hiv-antigenen und hiv-antikörpern |
| EP2281834B1 (en) | 1999-04-09 | 2015-03-04 | Zoetis P&U LLC | Attenuated Pasteurellaceae bacterium having a mutation in a virulence gene |
| US6790950B2 (en) | 1999-04-09 | 2004-09-14 | Pharmacia & Upjohn Company | Anti-bacterial vaccine compositions |
| US7192713B1 (en) * | 1999-05-18 | 2007-03-20 | President And Fellows Of Harvard College | Stabilized compounds having secondary structure motifs |
| AUPQ776100A0 (en) | 2000-05-26 | 2000-06-15 | Australian National University, The | Synthetic molecules and uses therefor |
| US6653102B2 (en) | 2000-10-17 | 2003-11-25 | Myriad Genetics, Inc. | Nucleic acid encoding a phosphatase 2C that interacts with Fe 65 |
| DK2332968T3 (en) | 2003-11-05 | 2016-08-22 | Dana Farber Cancer Inst Inc | Alpha-helix peptides suitable for activating or inhibiting cell death |
| WO2008008998A2 (en) | 2006-07-13 | 2008-01-17 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in signaling pathways |
| WO2008009000A2 (en) | 2006-07-13 | 2008-01-17 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in signaling pathways |
| CA2663188A1 (en) | 2006-09-11 | 2008-03-20 | The Board Of Trustees Of The University Of Illinois | Modifications of cupredoxin derived peptides and methods of use thereof |
| EP2073829B1 (en) | 2006-10-05 | 2012-06-20 | New York Blood Center, Inc. | Stabilized therapeutic small helical antiviral peptides |
| US8937154B2 (en) | 2006-10-05 | 2015-01-20 | New York Blood Center, Inc. | Stabilized therapeutic small helical antiviral peptides |
| PL2118123T3 (pl) | 2007-01-31 | 2016-06-30 | Dana Farber Cancer Inst Inc | Stabilizowane peptydy p53 i ich zastosowania |
| JP5078401B2 (ja) * | 2007-03-27 | 2012-11-21 | 株式会社Ａｄｅｋａ | 防水シート |
| US8921323B2 (en) | 2007-09-26 | 2014-12-30 | Dana Farber Cancer Institute, Inc. | Methods and compositions for modulating BCL-2 family polypeptides |
| CA2713089C (en) | 2008-01-23 | 2017-11-21 | Dana Farber Cancer Institute | Compositions and methods for the treatment of viral infections |
| JP2011522796A (ja) * | 2008-05-06 | 2011-08-04 | ニューヨーク ブラッド センター， インコーポレイテッド | 抗ウイルス細胞透過性ペプチド |
| JP6049260B2 (ja) | 2008-10-10 | 2016-12-21 | ダナ ファーバー キャンサー インスティテュート インコーポレイテッド | プロアポトーシスｂａｘ及びｂｃｌ−２ポリペプチドの化学モジュレータ |
-
2009
- 2009-05-05 JP JP2011508615A patent/JP2011522796A/ja active Pending
- 2009-05-05 CA CA2725227A patent/CA2725227A1/en not_active Abandoned
- 2009-05-05 EP EP09743518A patent/EP2283033A1/en not_active Withdrawn
- 2009-05-05 AU AU2009244400A patent/AU2009244400B2/en not_active Ceased
- 2009-05-05 WO PCT/US2009/042913 patent/WO2009137532A1/en not_active Ceased
- 2009-05-05 US US12/436,080 patent/US8324153B2/en not_active Expired - Fee Related
-
2012
- 2012-10-31 US US13/664,699 patent/US8933019B2/en active Active
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