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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| KR20130045914A (ko) * | 2010-08-03 | 2013-05-06 | 에프. 호프만-라 로슈 아게 | 만성 림프구성 백혈병(cll) 생체지표 |
| CA2807552A1 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP2857499A1 (en) | 2010-10-01 | 2015-04-08 | Moderna Therapeutics, 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 |
| HUE032100T2 (en) * | 2011-03-21 | 2017-08-28 | Valcuria Ab | A pharmaceutical composition comprising an HDAC inhibitor and a steroid and its use |
| CA2831613A1 (en) | 2011-03-31 | 2012-10-04 | Moderna Therapeutics, Inc. | 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 |
| PT3682905T (pt) | 2011-10-03 | 2022-04-07 | Modernatx Inc | Nucleósidos, nucleótidos e ácidos nucleicos modificados e respetivas utilizações |
| ES2923757T3 (es) | 2011-12-16 | 2022-09-30 | Modernatx Inc | Composiciones de ARNm modificado |
| WO2013151664A1 (en) | 2012-04-02 | 2013-10-10 | modeRNA Therapeutics | Modified polynucleotides for the production of proteins |
| US10501512B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides |
| 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 |
| US20140004131A1 (en) * | 2012-05-04 | 2014-01-02 | Novartis Ag | Antibody formulation |
| PT2922554T (pt) | 2012-11-26 | 2022-06-28 | Modernatx Inc | Arn modificado nas porções terminais |
| 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 |
| KR20160067219A (ko) | 2013-10-03 | 2016-06-13 | 모더나 세라퓨틱스, 인코포레이티드 | 저밀도 지단백질 수용체를 암호화하는 폴리뉴클레오타이드 |
| 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 |
| WO2016040294A2 (en) | 2014-09-09 | 2016-03-17 | Janssen Biotech, Inc. | Combination therapies with anti-cd38 antibodies |
| PE20171094A1 (es) | 2014-12-04 | 2017-08-07 | Janssen Biotech Inc | Anticuerpos anti-cd38 para el tratamiento de la leucemia linfoblastica aguda |
| WO2016094679A1 (en) | 2014-12-10 | 2016-06-16 | Regents Of The University Of Minnesota | Genetically modified cells, tissues, and organs for treating disease |
| WO2016115475A1 (en) * | 2015-01-18 | 2016-07-21 | 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 |
| CN107708734B (zh) | 2015-06-22 | 2022-01-11 | 詹森生物科技公司 | 用抗cd38抗体和生存素抑制剂联合治疗血红素恶性肿瘤 |
| US20170044265A1 (en) | 2015-06-24 | 2017-02-16 | Janssen Biotech, Inc. | Immune Modulation and Treatment of Solid Tumors with Antibodies that Specifically Bind CD38 |
| WO2017040932A1 (en) | 2015-09-04 | 2017-03-09 | Primatope Therapeutics Inc. | Humanized anti-cd40 antibodies and uses thereof |
| US10781261B2 (en) | 2015-11-03 | 2020-09-22 | Janssen Biotech, Inc. | Subcutaneous formulations of anti-CD38 antibodies and their uses |
| JP7027321B2 (ja) | 2015-11-03 | 2022-03-01 | ヤンセン バイオテツク，インコーポレーテツド | 抗ｃｄ３８抗体の皮下製剤及びその使用 |
| KR102379464B1 (ko) | 2016-06-20 | 2022-03-29 | 키맵 리미티드 | 항-pd-l1 항체 |
| WO2018002181A1 (en) | 2016-06-28 | 2018-01-04 | Umc Utrecht Holding B.V. | TREATMENT OF IgE-MEDIATED DISEASES WITH ANTIBODIES THAT SPECIFICALLY BIND CD38 |
| US11618787B2 (en) | 2017-10-31 | 2023-04-04 | Janssen Biotech, Inc. | Methods of treating high risk multiple myeloma |
| WO2019241730A2 (en) | 2018-06-15 | 2019-12-19 | Flagship Pioneering Innovations V, Inc. | Increasing immune activity through modulation of postcellular signaling factors |
| MA55805A (fr) | 2019-05-03 | 2022-03-09 | Flagship Pioneering Innovations V Inc | Métodes de modulation de l'activité immunitaire |
| JP2023509359A (ja) | 2019-12-17 | 2023-03-08 | フラグシップ パイオニアリング イノベーションズ ブイ，インコーポレーテッド | 鉄依存性細胞分解の誘導物質との併用抗癌療法 |
| CN116096906A (zh) | 2020-06-29 | 2023-05-09 | 旗舰创业创新五公司 | 工程化以促进萨诺传递的病毒及其在治疗癌症中的用途 |
| EP4313109A1 (en) | 2021-03-31 | 2024-02-07 | Flagship Pioneering Innovations V, Inc. | Thanotransmission polypeptides and their use in treating cancer |
| US20240207281A1 (en) * | 2021-04-21 | 2024-06-27 | Celgene Corporation | Methods of treating b-cell lymphoma using combination therapy |
| US20240316104A1 (en) | 2021-06-29 | 2024-09-26 | Flagship Pioneering Innovations V, Inc. | Immune cells engineered to promote thanotransmission and uses thereof |
| US12234294B2 (en) | 2021-11-05 | 2025-02-25 | Kiniksa Pharmaceuticals, Gmbh | Pharmaceutical composition of a humanized anti-CD40 antibody |
| CN117430704B (zh) * | 2022-07-22 | 2026-05-15 | 广东安普泽生物医药股份有限公司 | Cd40抗体或抗原结合片段及其应用 |
| 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 |
| US20070098718A1 (en) * | 2003-11-04 | 2007-05-03 | Chiron | Methods of therapy for b cell-related cancers |
| DK1680141T3 (da) * | 2003-11-04 | 2010-11-01 | Novartis Vaccines & Diagnostic | Fremgangsmåder til terapi til faste tumorer der udtrykker CD40-celleoverfladeantigenet |
| AU2004287879C1 (en) * | 2003-11-04 | 2011-05-26 | Novartis Vaccines And Diagnostics, Inc. | Antagonist anti-CD40 monoclonal antibodies and methods for their use |
| PT1684805E (pt) * | 2003-11-04 | 2010-10-26 | Novartis Vaccines & Diagnostic | Utilização de anticorpos monoclonais antagonistas anti-cd40 para o tratamento do mieloma múltiplo |
| RU2006141632A (ru) * | 2004-04-27 | 2008-06-10 | Новартис Вэксинес Энд Дайэгностикс, Инк. (Us) | Антагонистические моноклональные анти-cd40-антитела и способы их применения |
| AU2006241149A1 (en) * | 2005-04-26 | 2006-11-02 | Coley Pharmaceutical Gmbh | Modified oligoribonucleotide analogs with enhanced 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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| EP2211902A1 (en) | 2010-08-04 |
| AU2008323815A1 (en) | 2009-05-14 |
| US20110002934A1 (en) | 2011-01-06 |
| JP2011503098A (ja) | 2011-01-27 |
| RU2010123363A (ru) | 2011-12-20 |
| CA2705263A1 (en) | 2009-05-14 |
| KR20100088621A (ko) | 2010-08-09 |
| BRPI0820407A2 (pt) | 2015-05-26 |
| WO2009062054A1 (en) | 2009-05-14 |
| MX2010005099A (es) | 2010-05-27 |
| AU2008323815B2 (en) | 2013-09-19 |
| JP5559695B2 (ja) | 2014-07-23 |
| CN101970003A (zh) | 2011-02-09 |
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