ES2699532T3 - Métodos y composiciones para mejorar la terapia antiangiogénica con anti-integrinas - Google Patents
Métodos y composiciones para mejorar la terapia antiangiogénica con anti-integrinas Download PDFInfo
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| US201161466791P | 2011-03-23 | 2011-03-23 | |
| PCT/US2012/030204 WO2012129448A1 (en) | 2011-03-23 | 2012-03-22 | Methods and compositions for improving antiangiogenic therapy with anti-integrins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2699532T3 true ES2699532T3 (es) | 2019-02-11 |
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| ES12760157T Active ES2699532T3 (es) | 2011-03-23 | 2012-03-22 | Métodos y composiciones para mejorar la terapia antiangiogénica con anti-integrinas |
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| EP (1) | EP2688585B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2014523398A (cg-RX-API-DMAC7.html) |
| KR (1) | KR20140030153A (cg-RX-API-DMAC7.html) |
| CN (1) | CN103561761A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2012230809B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2830908C (cg-RX-API-DMAC7.html) |
| ES (1) | ES2699532T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2012129448A1 (cg-RX-API-DMAC7.html) |
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| EP2688585B1 (en) * | 2011-03-23 | 2018-09-05 | The Regents of The University of California | Methods and compositions for improving antiangiogenic therapy with anti-integrins |
| AU2013370467B2 (en) * | 2012-12-26 | 2018-10-04 | Oncosynergy, Inc. | Anti- integrin beta1 antibody compositions and methods of use thereof |
| EP3067698A1 (en) | 2015-03-11 | 2016-09-14 | Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) | Pd-ecgf as biomarker of cancer |
| EP3067369A1 (en) | 2015-03-11 | 2016-09-14 | Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) | Methods and compositions for the treatment of anti-angiogenic resistant cancer |
| WO2017032856A2 (en) | 2015-08-25 | 2017-03-02 | Histide Ag | Compounds for inducing tissue formation and uses thereof |
| CN109715191A (zh) * | 2015-09-17 | 2019-05-03 | 伊斯迪德股份公司 | 将赘生性细胞转化成非赘生性细胞的药物缔合物及其用途 |
| WO2017046229A1 (en) * | 2015-09-17 | 2017-03-23 | Histide Ag | Pharmaceutical association of growth factor receptor agonist and adhesion protein inhibitor for converting a neoplastic cell into a non-neoplastic cell and uses thereof |
| SG10201913366QA (en) * | 2015-09-17 | 2020-02-27 | Histide Ag | Pharmaceutical association for converting a neoplastic cell into a non-neoplastic cell and uses thereof |
| JP7222104B2 (ja) * | 2019-01-10 | 2023-02-14 | エスジー メディカル インコーポレイテッド | 抗ベータ１インテグリンヒト化抗体及びこれを含む癌治療用薬学組成物 |
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|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5272263A (en) * | 1989-04-28 | 1993-12-21 | Biogen, Inc. | DNA sequences encoding vascular cell adhesion molecules (VCAMS) |
| US6033665A (en) | 1989-09-27 | 2000-03-07 | Elan Pharmaceuticals, Inc. | Compositions and methods for modulating leukocyte adhesion to brain endothelial cells |
| US6165467A (en) | 1991-07-20 | 2000-12-26 | Yoshihide Hagiwara | Stabilized human monoclonal antibody preparation |
| US5840300A (en) | 1995-09-11 | 1998-11-24 | Trustees Of The University Of Pennsylvania | Methods and compositions comprising single chain recombinant antibodies |
| US5846536A (en) * | 1996-10-04 | 1998-12-08 | The Regents Of The University Of California | Restoration of normal phenotype in cancer cells |
| US6596276B1 (en) | 1997-09-30 | 2003-07-22 | Beth Israel Deaconess Medical Center | Method for inhibiting tumor angiogenesis in a living subject |
| EP2044955A3 (en) * | 1998-05-08 | 2009-04-29 | The Regents of the University of California | Methods for detecting and inhibiting angiogenesis |
| EP1158985B1 (en) | 1999-01-13 | 2011-12-28 | Bayer HealthCare LLC | OMEGA-CARBOXY ARYL SUBSTITUTED DIPHENYL UREAS AS p38 KINASE INHIBITORS |
| US7928239B2 (en) | 1999-01-13 | 2011-04-19 | Bayer Healthcare Llc | Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas |
| EP1140840B1 (en) | 1999-01-13 | 2006-03-22 | Bayer Pharmaceuticals Corp. | -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| US6949245B1 (en) | 1999-06-25 | 2005-09-27 | Genentech, Inc. | Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies |
| US6716410B1 (en) | 1999-10-26 | 2004-04-06 | The Regents Of The University Of California | Reagents and methods for diagnosing, imaging and treating atherosclerotic disease |
| JP3789066B2 (ja) | 1999-12-08 | 2006-06-21 | 三菱電機株式会社 | 液晶表示装置 |
| US8725620B2 (en) | 2000-07-10 | 2014-05-13 | Nobuyoshi Morimoto | System and method for negotiating improved terms for products and services being purchased through the internet |
| US6995162B2 (en) | 2001-01-12 | 2006-02-07 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
| US6878714B2 (en) | 2001-01-12 | 2005-04-12 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
| AU2002310122A1 (en) * | 2001-05-25 | 2002-12-09 | Human Genome Sciences, Inc. | Chemokine beta-1 fusion proteins |
| CA2453403C (en) | 2001-07-09 | 2013-10-08 | Elan Pharmaceuticals, Inc. | Methods of inhibiting amyloid toxicity |
| WO2003047523A2 (en) | 2001-12-04 | 2003-06-12 | Onyx Pharmaceuticals, Inc. | Raf-mek-erk pathway inhibitors to treat cancer |
| BRPI0412219B8 (pt) | 2003-07-23 | 2021-07-27 | Bayer Healthcare Llc | compostos ômega-carboxi aril difenil uréia fluoro substituídos e composições farmacêuticas compreendendo os referidos compostos |
| GEP20084439B (en) | 2004-01-23 | 2008-07-25 | Amgen Inc | Nitrogen-containing heterocyclic derivatives and pharmaceutical use thereof |
| WO2005117976A2 (en) * | 2004-06-03 | 2005-12-15 | The Regent Of The University Of California | Method of increasing radiation sensitivity by inhibition of beta one integrin |
| WO2007002543A2 (en) | 2005-06-23 | 2007-01-04 | Medimmune, Inc. | Antibody formulations having optimized aggregation and fragmentation profiles |
| AR059066A1 (es) | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| JP4997432B2 (ja) * | 2006-02-10 | 2012-08-08 | 学校法人慶應義塾 | 神経幹細胞の増殖抑制剤 |
| ZA200807754B (en) * | 2006-03-21 | 2009-12-30 | Genentech Inc | Combinatorial therapy involving alpha5beta1 antagonists |
| ES2544957T3 (es) * | 2006-03-21 | 2015-09-07 | Genentech, Inc. | Terapia combinada que implica antagonistas alfa5beta1 |
| EP2066689A4 (en) * | 2006-09-07 | 2010-04-28 | Univ South Florida | HYD1-PEPTIDE AS ANTICREMENT |
| WO2009009114A2 (en) * | 2007-07-12 | 2009-01-15 | Oncomed Pharmaceuticals, Inc. | Compositions and methods for treating and diagnosing cancer |
| MX2010000997A (es) * | 2007-07-27 | 2010-03-31 | Facet Biotech Corp | Combinaciones farmaceuticas que comprenden un inhibidor de tirosina cinasa y un anticuerpo contra integrina alfa 1 beta 5 (cd49b). |
| EP2060287B1 (de) * | 2007-11-14 | 2011-06-15 | BrainLAB AG | Medikamentenzuführungssystem für CED (Convection Enhanced Delivery)-Katheterinfusionen |
| EP2318017A1 (en) * | 2008-08-20 | 2011-05-11 | New York Blood Center, Inc. | Regulation of integrin surface expression |
| AU2009331529A1 (en) * | 2008-12-23 | 2011-08-11 | Astrazeneca Ab | Targeted binding agents directed to alpha5beta1 and uses therefor |
| TWI504409B (zh) * | 2009-03-25 | 2015-10-21 | Genentech Inc | 新穎抗－α５β１抗體及其用途 |
| EP2688585B1 (en) * | 2011-03-23 | 2018-09-05 | The Regents of The University of California | Methods and compositions for improving antiangiogenic therapy with anti-integrins |
| AU2013370467B2 (en) * | 2012-12-26 | 2018-10-04 | Oncosynergy, Inc. | Anti- integrin beta1 antibody compositions and methods of use thereof |
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- 2012-03-22 US US14/006,669 patent/US20140079637A1/en not_active Abandoned
- 2012-03-22 CA CA2830908A patent/CA2830908C/en active Active
- 2012-03-22 CN CN201280024596.8A patent/CN103561761A/zh active Pending
- 2012-03-22 WO PCT/US2012/030204 patent/WO2012129448A1/en not_active Ceased
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- 2012-03-22 KR KR1020137027236A patent/KR20140030153A/ko not_active Ceased
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2688585A4 (en) | 2015-05-06 |
| EP2688585B1 (en) | 2018-09-05 |
| WO2012129448A1 (en) | 2012-09-27 |
| CA2830908A1 (en) | 2012-09-27 |
| US20140079637A1 (en) | 2014-03-20 |
| US20180236073A1 (en) | 2018-08-23 |
| US11185585B2 (en) | 2021-11-30 |
| KR20140030153A (ko) | 2014-03-11 |
| AU2012230809A1 (en) | 2013-10-10 |
| CN103561761A (zh) | 2014-02-05 |
| AU2012230809B2 (en) | 2017-06-29 |
| US20220111045A1 (en) | 2022-04-14 |
| CA2830908C (en) | 2019-09-24 |
| JP2014523398A (ja) | 2014-09-11 |
| EP2688585A1 (en) | 2014-01-29 |
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