JP2005511636A - 自己免疫疾患の治療方法及びそれに関する試薬 - Google Patents
自己免疫疾患の治療方法及びそれに関する試薬 Download PDFInfo
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- JP2005511636A JP2005511636A JP2003546737A JP2003546737A JP2005511636A JP 2005511636 A JP2005511636 A JP 2005511636A JP 2003546737 A JP2003546737 A JP 2003546737A JP 2003546737 A JP2003546737 A JP 2003546737A JP 2005511636 A JP2005511636 A JP 2005511636A
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- alkyl
- alkenyl
- alkynyl
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| US33369101P | 2001-11-26 | 2001-11-26 | |
| PCT/US2002/038347 WO2003045228A2 (en) | 2001-11-26 | 2002-11-26 | Methods for treating autoimmune disorders, and reagents related thereto |
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| JP2010172410A Division JP2010248251A (ja) | 2001-11-26 | 2010-07-30 | 自己免疫疾患の治療方法及びそれに関する試薬 |
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| JP2005511636A true JP2005511636A (ja) | 2005-04-28 |
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| JP2014076508A Pending JP2014122251A (ja) | 2001-11-26 | 2014-04-02 | 自己免疫疾患の治療方法及びそれに関する試薬 |
| JP2016074086A Abandoned JP2016147895A (ja) | 2001-11-26 | 2016-04-01 | 自己免疫疾患の治療方法及びそれに関する試薬 |
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| JP2014076508A Pending JP2014122251A (ja) | 2001-11-26 | 2014-04-02 | 自己免疫疾患の治療方法及びそれに関する試薬 |
| JP2016074086A Abandoned JP2016147895A (ja) | 2001-11-26 | 2016-04-01 | 自己免疫疾患の治療方法及びそれに関する試薬 |
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| JP (4) | JP2005511636A (https=) |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999038501A2 (en) * | 1998-02-02 | 1999-08-05 | Trustees Of Tufts College | Method of regulating glucose metabolism, and reagents related thereto |
| WO2000010549A1 (en) * | 1998-08-21 | 2000-03-02 | Point Therapeutics, Inc. | Regulation of substrate activity |
| WO2001051641A1 (en) * | 2000-01-13 | 2001-07-19 | Tularik Inc. | Irak-4: compositions and methods of use |
| JP2001316390A (ja) * | 2000-02-29 | 2001-11-13 | Takeda Chem Ind Ltd | チエノピリジン誘導体、その製造法および用途 |
| JP2001316387A (ja) * | 2000-04-03 | 2001-11-13 | Pfizer Prod Inc | 抗炎症または鎮痛薬としてのピラゾール誘導体 |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1164225B (it) | 1983-05-13 | 1987-04-08 | Anic Spa | Analoghi retro-invertiti del pentapeptide potenziante la bradichina bpp5a e metodi per la loro preparazione |
| SE8702550D0 (sv) | 1987-06-18 | 1987-06-18 | Anders Grubb | Cysteinproteashemmare |
| US4935493A (en) | 1987-10-06 | 1990-06-19 | E. I. Du Pont De Nemours And Company | Protease inhibitors |
| ZA897515B (en) | 1988-10-07 | 1990-06-27 | Merrell Dow Pharma | Novel peptidase inhibitors |
| IT1227907B (it) | 1988-12-23 | 1991-05-14 | Eniricerche S P A Milano Sclav | Procedimento per la sintesi di peptidi retro-inversi e nuovi intermediin tale procedimento |
| JP2701932B2 (ja) | 1989-04-10 | 1998-01-21 | サントリー株式会社 | タンパク質分解酵素阻害剤 |
| EP0528858B1 (en) * | 1990-04-14 | 1997-01-22 | New England Medical Center Hospitals, Inc. | Inhibitors of dipeptidyl-aminopeptidase type iv |
| US5462928A (en) * | 1990-04-14 | 1995-10-31 | New England Medical Center Hospitals, Inc. | Inhibitors of dipeptidyl-aminopeptidase type IV |
| CA2121369C (en) | 1991-10-22 | 2003-04-29 | William W. Bachovchin | Inhibitors of dipeptidyl-aminopeptidase type iv |
| US6825169B1 (en) * | 1991-10-22 | 2004-11-30 | Trustees Of Tufts College | Inhibitors of dipeptidyl-aminopeptidase type IV |
| DK36392D0 (da) * | 1992-03-19 | 1992-03-19 | Novo Nordisk As | Anvendelse af kemisk forbindelse |
| US5296604A (en) | 1992-05-15 | 1994-03-22 | Miles Inc. | Proline derivatives and compositions for their use as inhibitors of HIV protease |
| IL111785A0 (en) | 1993-12-03 | 1995-01-24 | Ferring Bv | Dp-iv inhibitors and pharmaceutical compositions containing them |
| US5580979A (en) * | 1994-03-15 | 1996-12-03 | Trustees Of Tufts University | Phosphotyrosine peptidomimetics for inhibiting SH2 domain interactions |
| US5543396A (en) | 1994-04-28 | 1996-08-06 | Georgia Tech Research Corp. | Proline phosphonate derivatives |
| US5614649A (en) | 1994-11-14 | 1997-03-25 | Cephalon, Inc. | Multicatalytic protease inhibitors |
| US5834428A (en) * | 1995-04-14 | 1998-11-10 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
| FI974437A7 (fi) | 1995-06-06 | 1997-12-05 | Pfizer | Substituoituja N-(indoli-2-karbonyyli)amideja ja johdannaisia glykogee nifosforylaasi-inhibiittoreina |
| DE122010000020I1 (de) * | 1996-04-25 | 2010-07-08 | Prosidion Ltd | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
| US5783556A (en) * | 1996-08-13 | 1998-07-21 | Genentech, Inc. | Formulated insulin-containing composition |
| TW492957B (en) | 1996-11-07 | 2002-07-01 | Novartis Ag | N-substituted 2-cyanopyrrolidnes |
| US6011155A (en) * | 1996-11-07 | 2000-01-04 | Novartis Ag | N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| US5952301A (en) * | 1996-12-10 | 1999-09-14 | 1149336 Ontario Inc. | Compositions and methods for enhancing intestinal function |
| WO1999015183A1 (en) * | 1997-09-25 | 1999-04-01 | Proscript Inc. | PROTEASOME INHIBITORS, UBIQUITIN PATHWAY INHIBITORS OR AGENTS THAT INTERFERE WITH THE ACTIVATION OF NF-λB VIA THE UBIQUITIN PROTEASOME PATHWAY TO TREAT INFLAMMATORY AND AUTOIMMUNE DISEASES |
| ATE357509T1 (de) * | 1997-09-29 | 2007-04-15 | Point Therapeutics Inc | Stimulierung von hämatopoietischen zellen im vitro |
| IL139247A0 (en) * | 1998-05-04 | 2001-11-25 | Point Therapeutics Inc | Hematopoietic stimulation |
| JP2002517401A (ja) * | 1998-06-05 | 2002-06-18 | ポイント セラピューティクス， インコーポレイテッド | 環状ボロプロリン化合物 |
| US6979697B1 (en) * | 1998-08-21 | 2005-12-27 | Point Therapeutics, Inc. | Regulation of substrate activity |
| US6890904B1 (en) * | 1999-05-25 | 2005-05-10 | Point Therapeutics, Inc. | Anti-tumor agents |
| DE19940130A1 (de) * | 1999-08-24 | 2001-03-01 | Probiodrug Ges Fuer Arzneim | Neue Effektoren der Dipeptidyl Peptidase IV zur topischen Anwendung |
| JP2003535034A (ja) | 1999-11-12 | 2003-11-25 | ギルフォード ファーマシューティカルズ インコーポレイテッド | ジペプチジルペプチダーゼｉｖ阻害剤並びにジペプチジルペプチダーゼｉｖ阻害剤の製造及び使用法 |
| KR20080067009A (ko) * | 2000-03-31 | 2008-07-17 | 프로시디온 리미티드 | 디펩티딜 펩티다제 ⅳ 효소 활성 억제제를 포함하는약제학적 조성물 |
| GB0010188D0 (en) * | 2000-04-26 | 2000-06-14 | Ferring Bv | Inhibitors of dipeptidyl peptidase IV |
| DE10025464A1 (de) * | 2000-05-23 | 2001-12-06 | Inst Medizintechnologie Magdeb | Kombinierte Verwendung von Enzyminhibitoren zur Therapie von Autoimmunerkrankungen, bei Transplantationen und Tumorerkrankungen sowie Kombinationen von Enzyminhibitoren umfassende pharmazeutische Zubereitungen |
| EP1368349B1 (de) * | 2001-02-24 | 2007-02-14 | Boehringer Ingelheim Pharma GmbH & Co.KG | Xanthinderivate, deren herstellung und deren verwendung als arzneimittel |
| EP2316470A3 (en) * | 2001-11-26 | 2011-08-24 | Trustees Of Tufts College | Peptidomimetic inhibitors of post-proline cleaving enzymes |
| WO2004004661A2 (en) * | 2002-07-09 | 2004-01-15 | Point Therapeutics, Inc. | Boroproline compound combination therapy |
| ATE549028T1 (de) * | 2003-05-15 | 2012-03-15 | Tufts College | Stabile analoga von glp-1 |
| AU2005216970B2 (en) * | 2004-02-23 | 2011-07-07 | Trustees Of Tufts College | Inhibitors of dipeptidylpeptidase IV for regulating glucose metabolism |
| US20060063719A1 (en) * | 2004-09-21 | 2006-03-23 | Point Therapeutics, Inc. | Methods for treating diabetes |
| DE102012201584B4 (de) | 2012-02-03 | 2021-04-01 | Lear Corporation | Sitzschienenanordnung mit wählbaren Endanschlag-Positionen und Verfahren zum Ausbilden einer Sitzschienenanordnung |
-
2002
- 2002-11-26 WO PCT/US2002/038347 patent/WO2003045228A2/en not_active Ceased
- 2002-11-26 US US10/496,627 patent/US8410053B2/en not_active Expired - Fee Related
- 2002-11-26 EP EP14161169.9A patent/EP2769715A3/en not_active Ceased
- 2002-11-26 CA CA002466870A patent/CA2466870A1/en not_active Abandoned
- 2002-11-26 EP EP02795710A patent/EP1487471A4/en not_active Withdrawn
- 2002-11-26 JP JP2003546737A patent/JP2005511636A/ja active Pending
- 2002-11-26 AU AU2002360453A patent/AU2002360453C1/en not_active Ceased
-
2010
- 2010-07-30 JP JP2010172410A patent/JP2010248251A/ja active Pending
-
2012
- 2012-03-14 US US13/420,121 patent/US20120232004A1/en not_active Abandoned
-
2014
- 2014-04-02 JP JP2014076508A patent/JP2014122251A/ja active Pending
-
2016
- 2016-04-01 JP JP2016074086A patent/JP2016147895A/ja not_active Abandoned
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999038501A2 (en) * | 1998-02-02 | 1999-08-05 | Trustees Of Tufts College | Method of regulating glucose metabolism, and reagents related thereto |
| WO2000010549A1 (en) * | 1998-08-21 | 2000-03-02 | Point Therapeutics, Inc. | Regulation of substrate activity |
| WO2001051641A1 (en) * | 2000-01-13 | 2001-07-19 | Tularik Inc. | Irak-4: compositions and methods of use |
| JP2001316390A (ja) * | 2000-02-29 | 2001-11-13 | Takeda Chem Ind Ltd | チエノピリジン誘導体、その製造法および用途 |
| JP2001316387A (ja) * | 2000-04-03 | 2001-11-13 | Pfizer Prod Inc | 抗炎症または鎮痛薬としてのピラゾール誘導体 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US10202383B2 (en) | 2002-08-21 | 2019-02-12 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| US10023574B2 (en) | 2002-08-21 | 2018-07-17 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| JP2009521441A (ja) * | 2005-12-19 | 2009-06-04 | トラスティーズ オブ タフツ カレッジ | ソフトプロテアーゼ抑制剤およびそのプロソフト型 |
| US12178819B2 (en) | 2006-05-04 | 2024-12-31 | Boehringer Ingelheim International Gmbh | DPP IV inhibitor formulations |
| US11919903B2 (en) | 2006-05-04 | 2024-03-05 | Boehringer Ingelheim International Gmbh | Polymorphs |
| US11291668B2 (en) | 2006-05-04 | 2022-04-05 | Boehringer Ingelheim International Gmbh | Uses of DPP IV inhibitors |
| US11084819B2 (en) | 2006-05-04 | 2021-08-10 | Boehringer Ingelheim International Gmbh | Polymorphs |
| US10080754B2 (en) | 2006-05-04 | 2018-09-25 | Boehringer Ingelheim International Gmbh | Uses of DPP IV inhibitors |
| US10301313B2 (en) | 2006-05-04 | 2019-05-28 | Boehringer Ingelheim International Gmbh | Polymorphs |
| US10022379B2 (en) | 2008-04-03 | 2018-07-17 | Boehringer Ingelheim International Gmbh | DPP-IV inhibitor combined with a further antidiabetic agent, tablets comprising such formulations, their use and process for their preparation |
| US10973827B2 (en) | 2008-04-03 | 2021-04-13 | Boehringer Ingelheim International Gmbh | DPP-IV inhibitor combined with a further antidiabetic agent, tablets comprising such formulations, their use and process for their preparation |
| JP5493234B2 (ja) * | 2008-05-15 | 2014-05-14 | 国立大学法人 岡山大学 | Ｐｓｇｌ−１阻害によるメタボリックシンドロームの予防及び治療法 |
| US10034877B2 (en) | 2008-08-06 | 2018-07-31 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients inappropriate for metformin therapy |
| US11911388B2 (en) | 2008-10-16 | 2024-02-27 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral or non-oral antidiabetic drug |
| US10092571B2 (en) | 2009-11-27 | 2018-10-09 | Boehringer Ingelheim International Gmbh | Treatment of genotyped diabetic patients with DPP-IV inhibitors such as linagliptin |
| US10004747B2 (en) | 2010-05-05 | 2018-06-26 | Boehringer Ingelheim International Gmbh | Combination therapy |
| US11911387B2 (en) | 2010-11-15 | 2024-02-27 | Boehringer Ingelheim International Gmbh | Vasoprotective and cardioprotective antidiabetic therapy |
| US10195203B2 (en) | 2012-05-14 | 2019-02-05 | Boehringr Ingelheim International GmbH | Use of a DPP-4 inhibitor in podocytes related disorders and/or nephrotic syndrome |
| JP2015520155A (ja) * | 2012-05-14 | 2015-07-16 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｓｉｒｓ及び／又は敗血症の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体 |
| US12364700B2 (en) | 2016-06-10 | 2025-07-22 | Boehringer Ingelheim International Gmbh | Medical use of pharmaceutical combination or composition |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2769715A3 (en) | 2014-09-17 |
| EP1487471A4 (en) | 2010-03-10 |
| WO2003045228A2 (en) | 2003-06-05 |
| AU2002360453C1 (en) | 2009-06-18 |
| EP2769715A2 (en) | 2014-08-27 |
| AU2002360453B2 (en) | 2008-07-10 |
| JP2014122251A (ja) | 2014-07-03 |
| JP2010248251A (ja) | 2010-11-04 |
| EP1487471A2 (en) | 2004-12-22 |
| CA2466870A1 (en) | 2003-06-05 |
| WO2003045228A9 (en) | 2004-09-16 |
| US8410053B2 (en) | 2013-04-02 |
| US20050070459A1 (en) | 2005-03-31 |
| JP2016147895A (ja) | 2016-08-18 |
| WO2003045228A3 (en) | 2004-10-21 |
| AU2002360453A1 (en) | 2003-06-10 |
| US20120232004A1 (en) | 2012-09-13 |
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