CA3058458A1 - Compositions and methods for targeting and killing .alpha.-v.beta.-3-positive cancer stem cells (cscs) and treating drug resistant cancers - Google Patents
Compositions and methods for targeting and killing .alpha.-v.beta.-3-positive cancer stem cells (cscs) and treating drug resistant cancers Download PDFInfo
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- CA3058458A1 CA3058458A1 CA3058458A CA3058458A CA3058458A1 CA 3058458 A1 CA3058458 A1 CA 3058458A1 CA 3058458 A CA3058458 A CA 3058458A CA 3058458 A CA3058458 A CA 3058458A CA 3058458 A1 CA3058458 A1 CA 3058458A1
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- C07K16/2839—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily
- C07K16/2848—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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Landscapes
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US7858117B2 (en) | 2002-02-21 | 2010-12-28 | Novosom Ag | Amphoteric liposomes and their use |
| JP2005533001A (ja) * | 2002-03-04 | 2005-11-04 | メディミューン，インコーポレーテッド | インテグリンαｖβ３アンタゴニストを他の物質と併用投与する癌の予防または治療方法 |
| EP1547581A1 (en) | 2003-12-23 | 2005-06-29 | Vectron Therapeutics AG | Liposomal vaccine for the treatment of human hematological malignancies |
| CA2549966A1 (en) | 2003-12-24 | 2005-07-07 | Ltt Bio-Pharma Co., Ltd. | Drug-containing nanoparticle, process for producing the same and parenterally administered preparation from the nanoparticle |
| JP2007526322A (ja) | 2004-03-02 | 2007-09-13 | マサチューセッツ インスティテュート オブ テクノロジー | ナノセル薬物送達系 |
| EP1773298A1 (en) | 2004-08-06 | 2007-04-18 | Biospectrum, Inc. | Multiple layered liposome and preparation method thereof |
| EP1784424A4 (en) * | 2004-08-16 | 2009-03-18 | Medimmune Inc | EPH RECEPTOR BINDING FC VARIANTS HAVING CELLULAR CELLULAR ACTIVITY DEPENDENT ANTIBODIES |
| CN101506238B (zh) * | 2005-06-30 | 2013-11-06 | 森托科尔公司 | 具有提高治疗活性的方法和成分 |
| EP1937213B1 (en) | 2005-07-27 | 2017-10-25 | Protiva Biotherapeutics Inc. | Systems and methods for manufacturing liposomes |
| US20080088046A1 (en) | 2006-10-13 | 2008-04-17 | Steffen Panzner | Amphoteric liposomes, a method of formulating an amphoteric liposome and a method of loading an amphoteric liposome |
| JP5199108B2 (ja) * | 2005-11-14 | 2013-05-15 | ユニヴァーシティー オブ サザン カリフォルニア | インテグリン結合小分子 |
| US20080089928A1 (en) | 2006-06-13 | 2008-04-17 | Stavroula Sofou | Liposome drug carriers with ph-sensitivity |
| US20110319335A1 (en) * | 2010-06-23 | 2011-12-29 | Xiaodong Feng | Combined administration of integrin receptor antagonists for anti-angiogenic therapy |
| WO2012167028A2 (en) * | 2011-06-02 | 2012-12-06 | The Regents Of The University Of California | Compositions and methods for treating cancer and diseases and conditions responsive to cell growth inhibition |
| WO2013152313A1 (en) * | 2012-04-05 | 2013-10-10 | The Regents Of The University Of California | Compositions and methods for treating cancer and diseases and conditions responsive to growth factor inhibition |
| WO2015049280A1 (en) * | 2013-10-01 | 2015-04-09 | Medimmune Limited | Methods of treating and diagnosing alpha-v-beta-6 overexpressing cancer |
| KR102813659B1 (ko) * | 2013-11-11 | 2025-05-28 | 추가이 세이야쿠 가부시키가이샤 | 개변된 항체 가변영역을 포함하는 항원 결합 분자 |
| US11052089B2 (en) * | 2014-12-18 | 2021-07-06 | The Regents Of The University Of California | Methods for inhibiting alpha-v beta-3 expression on cancer stem cells and inhibiting progression to a cancer stem cell phenotype |
| AU2020324391A1 (en) * | 2019-08-02 | 2022-01-20 | The Regents Of The University Of California | Compositions and methods for targeting and killing alpha-v beta-3 -positive cancer stem cells (CSCS) and treating drug resistant and metastatic cancers |
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2018
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- 2018-03-30 MX MX2019011717A patent/MX2019011717A/es unknown
- 2018-03-30 CA CA3058458A patent/CA3058458A1/en active Pending
- 2018-03-30 US US16/499,623 patent/US20200109205A1/en not_active Abandoned
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- 2018-03-30 EP EP23203602.0A patent/EP4353318A3/en active Pending
- 2018-03-30 EA EA201992326A patent/EA201992326A1/ru unknown
- 2018-03-30 BR BR112019020451A patent/BR112019020451A2/pt unknown
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| EP3600422A4 (en) | 2021-01-13 |
| EA201992326A1 (ru) | 2020-03-13 |
| US20200109205A1 (en) | 2020-04-09 |
| WO2018183894A1 (en) | 2018-10-04 |
| JP2021095423A (ja) | 2021-06-24 |
| CN110662559A (zh) | 2020-01-07 |
| US20240067733A1 (en) | 2024-02-29 |
| KR102630070B1 (ko) | 2024-01-26 |
| MX2019011717A (es) | 2019-12-16 |
| EP3600422B1 (en) | 2023-10-18 |
| BR112019020451A2 (pt) | 2020-04-28 |
| AU2018243670A1 (en) | 2019-10-31 |
| EP3600422A1 (en) | 2020-02-05 |
| IL269746A (en) | 2019-11-28 |
| EP4353318A3 (en) | 2024-07-17 |
| JP2020512978A (ja) | 2020-04-30 |
| AU2018243670B2 (en) | 2025-05-01 |
| EP4353318A2 (en) | 2024-04-17 |
| KR20190133205A (ko) | 2019-12-02 |
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