公开(公告)号：US06544978B2

公开(公告)日：2003-04-08

申请号：US09915480

申请日：2001-07-27

申请人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

发明人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

IPC分类号： A61K3155

CPC分类号： C07D471/04 ,  A61K31/40 ,  A61K31/4015 ,  A61K31/445 ,  A61K31/5513 ,  A61K38/05 ,  C07C237/22 ,  C07C2603/32 ,  C07D223/18 ,  C07D307/33 ,  C07D311/76 ,  C07D471/06 ,  C07D471/08

摘要： Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

公开(公告)号：US06541466B2

公开(公告)日：2003-04-01

申请号：US09915362

申请日：2001-07-27

申请人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

发明人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

IPC分类号： A61K3155

CPC分类号： C07D471/04 ,  A61K31/40 ,  A61K31/4015 ,  A61K31/445 ,  A61K31/5513 ,  A61K38/05 ,  C07C237/22 ,  C07C2603/32 ,  C07D223/18 ,  C07D307/33 ,  C07D311/76 ,  C07D471/06 ,  C07D471/08

摘要： Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

公开(公告)号：US06951854B1

公开(公告)日：2005-10-04

申请号：US10951992

申请日：2004-09-29

申请人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

发明人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

IPC分类号： A61K31/40 ,  A61K31/4015 ,  A61K31/445 ,  A61K31/55 ,  A61K38/04 ,  A61K38/05 ,  A61P25/28 ,  C07D223/18 ,  C07D471/04 ,  C07D471/06 ,  C07D471/08

CPC分类号： C07D471/04 ,  A61K31/40 ,  A61K31/4015 ,  A61K31/445 ,  A61K31/5513 ,  A61K38/05 ,  C07C237/22 ,  C07C2603/32 ,  C07D223/18 ,  C07D307/33 ,  C07D311/76 ,  C07D471/06 ,  C07D471/08

摘要： Disclosed are compounds which inhibit β-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits β-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

公开(公告)号：US06683075B1

公开(公告)日：2004-01-27

申请号：US10336806

申请日：2003-01-06

申请人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

发明人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

IPC分类号： A61K3155

CPC分类号： C07D471/04 ,  A61K31/55 ,  C07D223/18 ,  C07D471/06 ,  C07D471/08

摘要： Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

摘要翻译： 公开了抑制β-淀粉样蛋白肽释放和/或其合成的化合物，因此具有治疗阿尔茨海默病的效用。 还公开了包含抑制β-淀粉样蛋白肽释放和/或其合成的化合物的药物组合物以及用这种药物组合物预防性和治疗性地治疗阿尔茨海默病的方法。

公开(公告)号：US06653303B1

公开(公告)日：2003-11-25

申请号：US10336824

申请日：2003-01-06

申请人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

发明人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

IPC分类号： A61K3155

CPC分类号： C07D471/04 ,  A61K31/40 ,  A61K31/4015 ,  A61K31/445 ,  A61K31/5513 ,  A61K38/05 ,  C07C237/22 ,  C07C2603/32 ,  C07D223/18 ,  C07D307/33 ,  C07D311/76 ,  C07D471/06 ,  C07D471/08

摘要： Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

公开(公告)号：US06559141B2

公开(公告)日：2003-05-06

申请号：US09915564

申请日：2001-07-27

申请人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

发明人： Jing Wu ,  Jay S. Tung ,  Eugene D. Thorsett ,  Michael A. Pleiss ,  Jeffrey S. Nissen ,  R. Jeffrey Neitz ,  Lee H. Latimer ,  Varghese John ,  Stephen Freedman ,  Thomas C. Britton ,  James A. Audia ,  Jon K. Reel ,  Thomas E. Mabry ,  Bruce A. Dressman ,  Cynthia L. Cwi ,  James J. Droste ,  Steven S. Henry ,  Stacey L. McDaniel ,  William Leonard Scott ,  Russell D. Stucky ,  Warren J. Porter

IPC分类号： A61K3155

CPC分类号： C07D471/04 ,  A61K31/40 ,  A61K31/4015 ,  A61K31/445 ,  A61K31/5513 ,  A61K38/05 ,  C07C237/22 ,  C07C2603/32 ,  C07D223/18 ,  C07D307/33 ,  C07D311/76 ,  C07D471/06 ,  C07D471/08

摘要： Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.

公开(公告)号：US20050215565A1

公开(公告)日：2005-09-29

申请号：US10763539

申请日：2004-01-26

申请人： Stephen Karlik ,  Michael Pleiss ,  Andrei Konradi ,  Francine Farouz ,  Christopher Semko ,  Darren Dressen ,  Elizabeth Messersmith ,  Stephen Freedman ,  Ted Yednock

发明人： Stephen Karlik ,  Michael Pleiss ,  Andrei Konradi ,  Francine Farouz ,  Christopher Semko ,  Darren Dressen ,  Elizabeth Messersmith ,  Stephen Freedman ,  Ted Yednock

IPC分类号： A61K20060101 ,  A61K6/00 ,  A61K31/10 ,  A61K31/16 ,  A61K31/185 ,  A61K31/195 ,  A61K31/198 ,  A61K31/21 ,  A61K31/216 ,  A61K31/381 ,  A61K31/395 ,  A61K31/397 ,  A61K31/40 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/427 ,  A61K31/44 ,  A61K31/445 ,  A61K31/47 ,  A61K31/472 ,  A61K31/495 ,  A61K31/496 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5375 ,  A61K31/54 ,  A61K31/541 ,  A61K31/56 ,  A61K38/21 ,  A61K39/395 ,  A61K45/06 ,  A61P25/00 ,  A61P29/00

CPC分类号： A61K45/06 ,  A61K31/10 ,  A61K31/16 ,  A61K31/185 ,  A61K31/195 ,  A61K31/21 ,  A61K31/496 ,  C07D417/14 ,  A61K2300/00

摘要： The application provides for methods and compositions for inhibiting demyelination, promoting remyelination and/or treating paralysis in a subject in need thereof. Preferably, such compositions include immunoglobulins (e.g., antibodies, antibody fragments, and recombinantly produced antibodies or fragments), polypeptides (e.g., soluble forms of the ligand proteins for integrins) and small molecules, which when administered in an effective amount inhibits demyelination and/or promotes remyelination in a patient. The compositions and methods described herein can also utilize other anti-inflammatory agents used to palliate conditions and diseases associated with demyelination.

公开(公告)号：US20050069541A1

公开(公告)日：2005-03-31

申请号：US10763424

申请日：2004-01-26

申请人： Stephen Karlik ,  Michael Pleiss ,  Andrei Konradi ,  Francine Farouz ,  Christopher Semko ,  Darren Dressen ,  Elizabeth Messersmith ,  Stephen Freedman ,  Ted Yednock

发明人： Stephen Karlik ,  Michael Pleiss ,  Andrei Konradi ,  Francine Farouz ,  Christopher Semko ,  Darren Dressen ,  Elizabeth Messersmith ,  Stephen Freedman ,  Ted Yednock

IPC分类号： A61K20060101 ,  A61K6/00 ,  A61K31/10 ,  A61K31/16 ,  A61K31/185 ,  A61K31/195 ,  A61K31/198 ,  A61K31/21 ,  A61K31/216 ,  A61K31/381 ,  A61K31/395 ,  A61K31/397 ,  A61K31/40 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/427 ,  A61K31/44 ,  A61K31/445 ,  A61K31/47 ,  A61K31/472 ,  A61K31/495 ,  A61K31/496 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5375 ,  A61K31/54 ,  A61K31/541 ,  A61K31/56 ,  A61K38/21 ,  A61K39/395 ,  A61K45/06 ,  A61P25/00 ,  A61P29/00

CPC分类号： A61K45/06 ,  A61K31/10 ,  A61K31/16 ,  A61K31/185 ,  A61K31/195 ,  A61K31/21 ,  A61K31/496 ,  A61P25/28 ,  C07D417/14 ,  A61K2300/00

摘要： The application provides for methods and compositions for inhibiting demyelination, promoting remyelination and/or treating paralysis in a subject in need thereof. Preferably, such compositions include immunoglobulins (e.g., antibodies, antibody fragments, and recombinantly produced antibodies or fragments), polypeptides (e.g., soluble forms of the ligand proteins for integrins) and small molecules, which when administered in an effective amount inhibits demyelination and/or promotes remyelination in a patient. The compositions and methods described herein can also utilize other anti-inflammatory agents used to palliate conditions and diseases associated with demyelination.

摘要翻译： 本申请提供了在有需要的受试者中抑制脱髓鞘，促进髓鞘再生和/或治疗麻痹的方法和组合物。 优选地，这样的组合物包括免疫球蛋白（例如，抗体，抗体片段和重组产生的抗体或片段），多肽（例如，用于整联蛋白的配体蛋白的可溶形式）和小分子，其以有效量施用时抑制脱髓鞘和/ 或促进患者的髓鞘再生。 本文所述的组合物和方法还可以利用用于缓解与脱髓鞘相关的病症和疾病的其它抗炎剂。

公开(公告)号：US20050074451A1

公开(公告)日：2005-04-07

申请号：US10875469

申请日：2004-06-25

申请人： Theodore Yednock ,  Stephen Freedman ,  Ivan Lieberburg ,  Michael Pleiss ,  Andrei Konradi ,  George Shopp ,  Elizabeth Messersmith

发明人： Theodore Yednock ,  Stephen Freedman ,  Ivan Lieberburg ,  Michael Pleiss ,  Andrei Konradi ,  George Shopp ,  Elizabeth Messersmith

IPC分类号： A61K20060101 ,  A61K31/16 ,  A61K31/18 ,  A61K31/195 ,  A61K31/40 ,  A61K31/415 ,  A61K31/425 ,  A61K31/44 ,  A61K31/519 ,  A61K31/525 ,  A61K38/00 ,  A61K39/00 ,  A61K39/395

CPC分类号： A61K31/519 ,  A61K39/39541 ,  A61K2300/00

摘要： This application relates to methods and compositions for treating rheumatoid arthritis by administering a combination therapy comprising methotrexate and an antibody to alpha-4 integrin or an immunologically active antigen binding fragment in therapeutically effective amounts. The application also relates generally to methods and compositions for treating rheumatoid arthritis by administering a combination therapy comprising methotrexate and small molecule alpha-4 integrin antagonist that inhibits the alpha-4 integrin (α4 integrin) interaction with VCAM-1. The invention further relates to methods of preparing the compounds and methods of using the compounds and compositions.

公开(公告)号：US20050065192A1

公开(公告)日：2005-03-24

申请号：US10875282

申请日：2004-06-25

申请人： Theodore Yednock ,  Stephen Freedman ,  Ivan Lieberburg ,  Michael Pleiss ,  Andrei Konradi ,  George Shopp ,  Elizabeth Messersmith

发明人： Theodore Yednock ,  Stephen Freedman ,  Ivan Lieberburg ,  Michael Pleiss ,  Andrei Konradi ,  George Shopp ,  Elizabeth Messersmith

IPC分类号： A61K20060101 ,  A61K31/16 ,  A61K31/18 ,  A61K31/195 ,  A61K31/40 ,  A61K31/415 ,  A61K31/425 ,  A61K31/44 ,  A61K31/519 ,  A61K31/525 ,  A61K38/00 ,  A61K39/00 ,  A61K39/395

CPC分类号： A61K31/519 ,  A61K39/39541 ,  A61K2300/00

摘要： This application relates to methods and compositions for treating rheumatoid arthritis by administering a combination therapy comprising methotrexate and an antibody to alpha-4 integrin or an immunologically active antigen binding fragment in therapeutically effective amounts. The application also relates generally to methods and compositions for treating rheumatoid arthritis by administering a combination therapy comprising methotrexate and small molecule alpha-4 integrin antagonist that inhibits the alpha-4 integrin (α4 integrin) interaction with VCAM-1. The invention further relates to methods of preparing the compounds and methods of using the compounds and compositions.

摘要翻译： 本申请涉及通过以治疗有效量施用包含甲氨蝶呤和α-4整联蛋白或免疫活性抗原结合片段的抗体的组合疗法来治疗类风湿性关节炎的方法和组合物。 该申请还通常涉及通过施用包含甲氨蝶呤和抑制与α-4整联蛋白（α4整联蛋白）与VCAM-1相互作用的小分子α-4整联蛋白拮抗剂的组合疗法来治疗类风湿性关节炎的方法和组合物。 本发明还涉及制备化合物的方法和使用该化合物和组合物的方法。