RU2625222C2 - Комбинированная терапия антителом к cd19 и азотистым ипритом - Google Patents
Комбинированная терапия антителом к cd19 и азотистым ипритом Download PDFInfo
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- RU2625222C2 RU2625222C2 RU2014103492A RU2014103492A RU2625222C2 RU 2625222 C2 RU2625222 C2 RU 2625222C2 RU 2014103492 A RU2014103492 A RU 2014103492A RU 2014103492 A RU2014103492 A RU 2014103492A RU 2625222 C2 RU2625222 C2 RU 2625222C2
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—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 immunoglobulin superfamily
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- C07K—PEPTIDES
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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- A—HUMAN NECESSITIES
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| US20170137516A1 (en) * | 2014-06-16 | 2017-05-18 | Xencor, Inc. | Treatment for chronic lymphocytic leukemia (cll) |
| SMT201900647T1 (it) * | 2015-05-26 | 2020-01-14 | Morphosys Ag | Combinazione di un anticorpo anti-cd19 e un inibitore della tirosina chinasi di bruton e suoi usi |
| WO2017032679A1 (en) * | 2015-08-21 | 2017-03-02 | Morphosys Ag | Combinations and uses thereof |
| AU2017244108B2 (en) | 2016-03-29 | 2021-03-18 | University Of Southern California | Chimeric antigen receptors targeting cancer |
| LT3916392T (lt) * | 2016-05-30 | 2024-08-26 | Incyte Corporation | Pacientų gydymo anti-cd19 terapinės naudos prognozavimo būdai |
| AU2017348624B2 (en) | 2016-10-28 | 2024-09-26 | Incyte Corporation | Combination of anti CD19 antibody with a BCL-2 inhibitor and uses thereof |
| BR112019011277A2 (pt) | 2016-12-02 | 2019-10-22 | University Of Southern California | polinucleotídeo, sistema de expressão recombinante, vetor, polipeptídeo, célula recombinante, polipeptídeo de receptor imune sintético isolado ou heterodímero de polipeptídeo, célula efetora imune ou célula-tronco, população de células imunes ou efetoras, métodos de fabricação de uma célula efetora imune que expressa sir, de geração de uma população de células modificadas por rna, de fornecimento de imunidade antidoença e de tratamento ou prevenção de uma doença, composição, uso ou método, kit, e, sequência de aminoácidos. |
| BR112019025034A2 (pt) | 2017-05-31 | 2020-06-30 | Morphosys Ag | combinação |
| KR20200030337A (ko) | 2018-09-12 | 2020-03-20 | 주식회사 녹십자랩셀 | 종양 치료를 위한 항-cd 19 항체 및 자연살해세포를 포함하는 약학적 조합물 |
| US20230357392A1 (en) * | 2021-12-22 | 2023-11-09 | Morphosys Ag | Treatment Paradigm for an Anti-CD19 Antibody Therapy |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2228202C2 (ru) * | 1998-04-21 | 2004-05-10 | Микромет Аг | Cd19xcd3-специфические полипептиды и их применение |
| WO2007076950A1 (en) * | 2005-12-30 | 2007-07-12 | Merck Patent Gmbh | Anti-cd19 antibodies with reduced immunogenicity |
| WO2008022152A2 (en) * | 2006-08-14 | 2008-02-21 | Xencor, Inc. | Optimized antibodies that target cd19 |
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| JPS60500673A (ja) | 1983-03-08 | 1985-05-09 | コモンウエルス セラム ラボラトリ−ズ コミツシヨン | 抗原活性を有するアミノ酸配列 |
| US5686072A (en) | 1992-06-17 | 1997-11-11 | Board Of Regents, The University Of Texas | Epitope-specific monoclonal antibodies and immunotoxins and uses thereof |
| AU777970C (en) * | 1999-05-07 | 2006-08-17 | F. Hoffman-La Roche Ag | Treatment of autoimmune diseases with antagonists which bind to B cell surface markers |
| WO2002022212A2 (en) | 2000-09-18 | 2002-03-21 | Idec Pharmaceuticals Corporation | Combination therapy for treatment of autoimmune diseases using b cell depleting/immunoregulatory antibody combination |
| US7771951B2 (en) | 2001-12-03 | 2010-08-10 | Amgen Fremont Inc. | Antibody categorization based on binding characteristics |
| US20080260731A1 (en) * | 2002-03-01 | 2008-10-23 | Bernett Matthew J | Optimized antibodies that target cd19 |
| US7109304B2 (en) | 2003-07-31 | 2006-09-19 | Immunomedics, Inc. | Humanized anti-CD19 antibodies |
| US7902338B2 (en) | 2003-07-31 | 2011-03-08 | Immunomedics, Inc. | Anti-CD19 antibodies |
| CA2585659A1 (en) | 2004-11-05 | 2006-06-22 | Cephalon, Inc. | Cancer treatments |
| JP5215180B2 (ja) | 2005-06-20 | 2013-06-19 | メダレックス インコーポレーティッド | Ｃｄ１９抗体およびその使用法 |
| US8323653B2 (en) | 2006-09-08 | 2012-12-04 | Medimmune, Llc | Humanized anti-CD19 antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
| ES2659517T3 (es) | 2007-05-30 | 2018-03-16 | Xencor, Inc. | Métodos y composiciones para inhibir células que expresan CD32B |
| SI2211904T1 (sl) | 2007-10-19 | 2016-12-30 | Seattle Genetics, Inc. | CD19 vezavna sredstva in njihove uporabe |
| JP2012515217A (ja) * | 2009-01-16 | 2012-07-05 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | ベンダムスチンおよび抗−ｃｄ２０抗体の組合せを用いた癌治療 |
| CN102421800A (zh) | 2009-02-23 | 2012-04-18 | 格兰马克药品股份有限公司 | 结合cd19的人源化抗体及其用途 |
| AU2010263272C1 (en) | 2009-06-24 | 2016-02-11 | The Feinstein Institute For Medical Research | Method for treating chronic lymphocytic leukemia |
| TWI409079B (zh) * | 2009-08-14 | 2013-09-21 | Roche Glycart Ag | 非典型岩藻醣化ｃｄ２０抗體與苯達莫斯汀（ｂｅｎｄａｍｕｓｔｉｎｅ）之組合療法 |
| RU2012109451A (ru) * | 2009-08-14 | 2013-09-27 | Роше Гликарт Аг | Комбинированная терапия на основе афукозилированного антитела к cd20 в сочетании с флударабином и/или митоксантроном |
| CN102711479A (zh) * | 2009-11-06 | 2012-10-03 | 无限药品股份有限公司 | Hedgehog通道抑制剂的口服制剂 |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2228202C2 (ru) * | 1998-04-21 | 2004-05-10 | Микромет Аг | Cd19xcd3-специфические полипептиды и их применение |
| WO2007076950A1 (en) * | 2005-12-30 | 2007-07-12 | Merck Patent Gmbh | Anti-cd19 antibodies with reduced immunogenicity |
| WO2008022152A2 (en) * | 2006-08-14 | 2008-02-21 | Xencor, Inc. | Optimized antibodies that target cd19 |
Non-Patent Citations (1)
| Title |
|---|
| KALOS M. et al., T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia, SCIENCE TRANSLATIONAL MEDICINE, 10 Aug 2011, Vol. 3, Issue 95, pp. 95ra73. * |
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