JP2005504517A - ＣＤ４４ｖ６特異的抗体 - Google Patents
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- JP2005504517A JP2005504517A JP2002592353A JP2002592353A JP2005504517A JP 2005504517 A JP2005504517 A JP 2005504517A JP 2002592353 A JP2002592353 A JP 2002592353A JP 2002592353 A JP2002592353 A JP 2002592353A JP 2005504517 A JP2005504517 A JP 2005504517A
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Cited By (1)
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| JP2023516080A (ja) * | 2020-03-06 | 2023-04-17 | ジーオー セラピューティクス，インコーポレイテッド | 抗グリコｃｄ４４抗体およびその使用 |
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| US20050100542A1 (en) | 1999-10-08 | 2005-05-12 | Young David S. | Cytotoxicity mediation of cells evidencing surface expression of CD44 |
| US8071072B2 (en) | 1999-10-08 | 2011-12-06 | Hoffmann-La Roche Inc. | Cytotoxicity mediation of cells evidencing surface expression of CD44 |
| US7947496B2 (en) | 1999-10-08 | 2011-05-24 | Hoffmann-La Roche Inc. | Cytotoxicity mediation of cells evidencing surface expression of CD44 |
| US8048416B2 (en) | 1999-10-08 | 2011-11-01 | Hoffmann-La Roche Inc. | Cytotoxicity mediation of cells evidencing surface expression of CD44 |
| US7189397B2 (en) | 1999-10-08 | 2007-03-13 | Arius Research Inc. | Cytotoxicity mediation of cells evidencing surface expression of CD44 |
| US7084257B2 (en) | 2001-10-05 | 2006-08-01 | Amgen Inc. | Fully human antibody Fab fragments with human interferon-gamma neutralizing activity |
| AU2005214331B2 (en) | 2004-02-12 | 2011-09-15 | Eisai, Inc. | Monoclonal antibodies that specifically bind to folate receptor alpha |
| ES2429340T3 (es) | 2005-03-10 | 2013-11-14 | Morphotek, Inc. | Anticuerpos anti-mesotelina |
| AU2006241099B2 (en) | 2005-04-22 | 2012-04-19 | Eisai, Inc. | Antibodies with immune effector activity and that internalize in folate receptor alpha-positive cells |
| DK2167038T3 (en) * | 2007-06-13 | 2018-08-06 | Zymogenetics Inc | USING TACI-IG FUSION PROTEIN AS ATACICEPT TO PREPARE A MEDICINE FOR TREATING LUPUS ERYTHEMATOSUS |
| EP2009028A1 (en) * | 2007-06-27 | 2008-12-31 | Monoclonal Antibodies Therapeutics | Combination of a conventional anti-cancer treatment with anti-CD44 antibody administration for treating solid tumors |
| AU2011212485B2 (en) | 2010-02-04 | 2014-04-17 | University Of Miami | A monoclonal antibody to CD44 for use in the treatment of head and neck squamous cell carcinoma |
| CN102337298B (zh) * | 2011-08-19 | 2013-11-06 | 黄开红 | 一种输送siRNA的免疫纳米载体及其制备方法和应用 |
| US20140335084A1 (en) | 2011-12-06 | 2014-11-13 | Hoffmann-La Roche Inc. | Antibody formulation |
| WO2017215637A1 (zh) * | 2016-06-15 | 2017-12-21 | 李翀 | 一种人子宫内膜癌的标志物、抗体及其应用 |
| CN107556388A (zh) * | 2016-06-30 | 2018-01-09 | 中国科学院深圳先进技术研究院 | 抗CD44v6和CD3特异性双靶向抗体、含该双靶向抗体表达盒的微环DNA及应用 |
| US20250326855A1 (en) * | 2021-03-05 | 2025-10-23 | Go Therapeutics, Inc. | Anti-glyco-cd44 antibodies and their uses |
Family Cites Families (7)
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| IL162181A (en) * | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| US5530101A (en) * | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| EP0438310A1 (en) * | 1990-01-19 | 1991-07-24 | Merck & Co. Inc. | Method for producing recombinant immunoglobuline |
| GB9020282D0 (en) * | 1990-09-17 | 1990-10-31 | Gorman Scott D | Altered antibodies and their preparation |
| WO1994012631A1 (en) * | 1992-11-20 | 1994-06-09 | Isis Innovation Limited | Peptide corresponding to cd44 exon 6, antibodies specific for said peptide and use of these antibodies for diagnosis of tumors |
| UA58482C2 (uk) * | 1994-06-08 | 2003-08-15 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | Моноклональне антитіло vff-18 проти сd44v6 і його фрагменти |
| UY24389A1 (es) * | 1995-12-06 | 2001-10-25 | Karlsruhe Forschzent | Composición farmacéutica para el tratamiento de carcinoma de epitelio plano |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023516080A (ja) * | 2020-03-06 | 2023-04-17 | ジーオー セラピューティクス，インコーポレイテッド | 抗グリコｃｄ４４抗体およびその使用 |
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| EA200301169A1 (ru) | 2004-06-24 |
| CN1541226A (zh) | 2004-10-27 |
| PE20021098A1 (es) | 2003-02-11 |
| EE200300569A (et) | 2004-04-15 |
| CZ20033476A3 (cs) | 2004-05-12 |
| YU91403A (sh) | 2006-05-25 |
| AR036154A1 (es) | 2004-08-18 |
| EP1397387A1 (en) | 2004-03-17 |
| WO2002094879A1 (en) | 2002-11-28 |
| MXPA03010523A (es) | 2004-07-01 |
| ECSP034838A (es) | 2003-12-24 |
| ZA200307365B (en) | 2004-05-10 |
| CA2443437A1 (en) | 2002-11-28 |
| HUP0400030A3 (en) | 2006-02-28 |
| PL365735A1 (en) | 2005-01-10 |
| BR0210905A (pt) | 2004-06-08 |
| HUP0400030A2 (hu) | 2004-04-28 |
| SK15592003A3 (sk) | 2004-06-08 |
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