RU2491095C2 - Применения анти-cd40-антител - Google Patents
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- RU2491095C2 RU2491095C2 RU2010123363/15A RU2010123363A RU2491095C2 RU 2491095 C2 RU2491095 C2 RU 2491095C2 RU 2010123363/15 A RU2010123363/15 A RU 2010123363/15A RU 2010123363 A RU2010123363 A RU 2010123363A RU 2491095 C2 RU2491095 C2 RU 2491095C2
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| MX2013001302A (es) * | 2010-08-03 | 2013-03-08 | Hoffmann La Roche | Biomarcadores de leucemia linfocitica (cll). |
| CA2807552A1 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP3431485B2 (en) | 2010-10-01 | 2024-09-04 | ModernaTX, Inc. | Engineered nucleic acids and methods of use thereof |
| HUE065915T2 (hu) | 2011-03-11 | 2024-06-28 | Beth Israel Deaconess Medical Ct Inc | Anti-CD40 antitestek és alkalmazásaik |
| ES2627020T3 (es) * | 2011-03-21 | 2017-07-26 | Valcuria Ab | Composición farmacéutica que comprende un inhibidor de HDAC y un esteroide y el uso de la misma |
| WO2012135805A2 (en) | 2011-03-31 | 2012-10-04 | modeRNA Therapeutics | Delivery and formulation of engineered nucleic acids |
| US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP2763701B1 (en) | 2011-10-03 | 2018-12-19 | Moderna Therapeutics, Inc. | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
| KR20140102759A (ko) | 2011-12-16 | 2014-08-22 | 모더나 세라퓨틱스, 인코포레이티드 | 변형된 뉴클레오사이드, 뉴클레오타이드 및 핵산 조성물 |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| DE18200782T1 (de) | 2012-04-02 | 2021-10-21 | Modernatx, Inc. | Modifizierte polynukleotide zur herstellung von proteinen im zusammenhang mit erkrankungen beim menschen |
| US9878056B2 (en) | 2012-04-02 | 2018-01-30 | Modernatx, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
| US20140004131A1 (en) | 2012-05-04 | 2014-01-02 | Novartis Ag | Antibody formulation |
| CA2892529C (en) | 2012-11-26 | 2023-04-25 | Moderna Therapeutics, Inc. | Terminally modified rna |
| US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
| US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
| EA201690675A1 (ru) | 2013-10-03 | 2016-08-31 | Модерна Терапьютикс, Инк. | Полинуклеотиды, кодирующие рецептор липопротеинов низкой плотности |
| US9732154B2 (en) | 2014-02-28 | 2017-08-15 | Janssen Biotech, Inc. | Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia |
| US9603927B2 (en) * | 2014-02-28 | 2017-03-28 | Janssen Biotech, Inc. | Combination therapies with anti-CD38 antibodies |
| MY192918A (en) | 2014-09-09 | 2022-09-15 | Janssen Biotech Inc | Combination therapies with anti-cd38 antibodies |
| EP3227338A4 (en) | 2014-12-04 | 2018-05-16 | Janssen Biotech, Inc. | Anti-cd38 antibodies for treatment of acute myeloid leukemia |
| AU2015360502A1 (en) | 2014-12-10 | 2017-06-29 | Regents Of The University Of Minnesota | Genetically modified cells, tissues, and organs for treating disease |
| US20180264112A1 (en) * | 2015-01-18 | 2018-09-20 | Biogen Ma Inc. | Anti-CD40 Antibody Formulations |
| CR20170526A (es) | 2015-05-20 | 2018-04-03 | Janssen Biotech Inc | ANTICUERPOS ANTI-CD38 PARA EL TRATAMIENTO DE AMILOIDOSIS DE CADENA LIGERA y OTRAS ENFERMEDADES MALIGNAS HEMATOLÓGICAS POSITIVAS PARA CD38 |
| MY192978A (en) | 2015-06-22 | 2022-09-20 | Janssen Biotech Inc | Combination therapies for heme malignancies with anti-cd38 antibodies and survivin inhibitors |
| US20170044265A1 (en) | 2015-06-24 | 2017-02-16 | Janssen Biotech, Inc. | Immune Modulation and Treatment of Solid Tumors with Antibodies that Specifically Bind CD38 |
| EP3307322B1 (en) | 2015-09-04 | 2021-02-17 | Primatope Therapeutics Inc. | Humanized anti-cd40 antibodies and uses thereof |
| PL3827845T3 (pl) | 2015-11-03 | 2022-07-11 | Janssen Biotech, Inc. | Formulacje podskórne przeciwciał anty-cd38 i ich zastosowania |
| US10781261B2 (en) | 2015-11-03 | 2020-09-22 | Janssen Biotech, Inc. | Subcutaneous formulations of anti-CD38 antibodies and their uses |
| BR112018076260A2 (pt) | 2016-06-20 | 2019-03-26 | Kymab Limited | anticorpo ou fragmento do mesmo que se liga especificamente a hpd-l1, anticorpo biespecífico ou proteína de fusão, uso de um anticorpo ou fragmento, método, composição farmacêutica, método de modulação, método de inibição, método de tratamento, ácido nucleico, vetor, hospedeiro e imunocitocina |
| CA3079242A1 (en) | 2017-10-31 | 2019-05-09 | Janssen Biotech, Inc. | Methods of treating high risk multiple myeloma |
| KR20210035805A (ko) | 2018-06-15 | 2021-04-01 | 플래그쉽 파이어니어링 이노베이션스 브이, 인크. | 세포후 신호전달 인자의 조절을 통한 면역 활성의 증가 |
| MA55805A (fr) | 2019-05-03 | 2022-03-09 | Flagship Pioneering Innovations V Inc | Métodes de modulation de l'activité immunitaire |
| US20230114107A1 (en) | 2019-12-17 | 2023-04-13 | Flagship Pioneering Innovations V, Inc. | Combination anti-cancer therapies with inducers of iron-dependent cellular disassembly |
| US20230355804A1 (en) | 2020-06-29 | 2023-11-09 | Flagship Pioneering Innovations V, Inc. | Viruses engineered to promote thanotransmission and their use in treating cancer |
| CA3214085A1 (en) | 2021-03-31 | 2022-10-06 | Darby Rye Schmidt | Thanotransmission polypeptides and their use in treating cancer |
| KR20240026507A (ko) | 2021-06-29 | 2024-02-28 | 플래그쉽 파이어니어링 이노베이션스 브이, 인크. | 타노트랜스미션을 촉진시키도록 엔지니어링된 면역 세포 및 이의 용도 |
| US12234294B2 (en) | 2021-11-05 | 2025-02-25 | Kiniksa Pharmaceuticals, Gmbh | Pharmaceutical composition of a humanized anti-CD40 antibody |
| WO2024077191A1 (en) | 2022-10-05 | 2024-04-11 | Flagship Pioneering Innovations V, Inc. | Nucleic acid molecules encoding trif and additionalpolypeptides and their use in treating cancer |
| WO2024151687A1 (en) | 2023-01-09 | 2024-07-18 | Flagship Pioneering Innovations V, Inc. | Genetic switches and their use in treating cancer |
| WO2025031434A1 (zh) * | 2023-08-08 | 2025-02-13 | 北京志道生物科技有限公司 | 经修饰的细胞因子与cd40激动剂的联用组合物及其抗肿瘤用途 |
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| RU2005103824A (ru) * | 2002-07-15 | 2005-08-27 | Дженентек, Инк. (Us) | Способы идентификации опухолей, восприимчивых к лечению антителами против erbb2 |
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| WO2002028481A2 (en) * | 2000-10-02 | 2002-04-11 | Chiron Corporation | Methods of therapy for b-cell malignancies using antagonist anti-cd40 antibodies |
| US20030180292A1 (en) * | 2002-03-14 | 2003-09-25 | Idec Pharmaceuticals | Treatment of B cell malignancies using anti-CD40L antibodies in combination with anti-CD20 antibodies and/or chemotherapeutics and radiotherapy |
| DK1684805T3 (da) * | 2003-11-04 | 2010-10-04 | Novartis Vaccines & Diagnostic | Anvendelse af antagonist anti-CD40-monoklonale antistoffer til behandling af multipel myeloma |
| RS53073B (sr) * | 2003-11-04 | 2014-04-30 | Novartis Vaccines And Diagnostics Inc. | Upotreba antagonističkih anti-cd40 monoklonska antitela |
| PT1684869E (pt) * | 2003-11-04 | 2011-09-16 | Novartis Vaccines & Diagnostic | Métodos de terapêutica para cancros relacionados com células b |
| EP2301575A1 (en) * | 2003-11-04 | 2011-03-30 | Novartis Vaccines and Diagnostics, Inc. | Methods of therapy for solid tumors expressing the CD40 cell-surface antigen |
| KR20070026522A (ko) * | 2004-04-27 | 2007-03-08 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 길항제 항-ｃｄ40 모노클론 항체 및 이들의 사용 방법 |
| WO2006116458A2 (en) * | 2005-04-26 | 2006-11-02 | Coley Pharmaceutical Gmbh | Modified oligoribonucleotide analogs with enhances immunostimulatory activity |
| MX2008007140A (es) * | 2005-12-09 | 2009-03-04 | Seattle Genetics Inc | Metodos para utilizar agentes de union a cd40. |
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| RU2005103824A (ru) * | 2002-07-15 | 2005-08-27 | Дженентек, Инк. (Us) | Способы идентификации опухолей, восприимчивых к лечению антителами против erbb2 |
Non-Patent Citations (1)
| Title |
|---|
| Mohammad RM. et al. The addition of bryostatin 1 to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy improves response in a CHOP-resistant human diffuse large cell lymphoma xenograft model// Clin Cancer Res. 2000 Dec; 6(12):4950-6. * |
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| US20110002934A1 (en) | 2011-01-06 |
| JP2011503098A (ja) | 2011-01-27 |
| JP5559695B2 (ja) | 2014-07-23 |
| MX2010005099A (es) | 2010-05-27 |
| BRPI0820407A2 (pt) | 2015-05-26 |
| AU2008323815A1 (en) | 2009-05-14 |
| EP2211902A1 (en) | 2010-08-04 |
| WO2009062054A1 (en) | 2009-05-14 |
| KR20100088621A (ko) | 2010-08-09 |
| CN101970003A (zh) | 2011-02-09 |
| AU2008323815B2 (en) | 2013-09-19 |
| RU2010123363A (ru) | 2011-12-20 |
| CA2705263A1 (en) | 2009-05-14 |
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