CA2904644C - Human antibodies to grem1 - Google Patents
Human antibodies to grem1 Download PDFInfo
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- CA2904644C CA2904644C CA2904644A CA2904644A CA2904644C CA 2904644 C CA2904644 C CA 2904644C CA 2904644 A CA2904644 A CA 2904644A CA 2904644 A CA2904644 A CA 2904644A CA 2904644 C CA2904644 C CA 2904644C
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- grem1
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| US61/883,218 | 2013-09-27 | ||
| PCT/US2014/021471 WO2014159010A1 (en) | 2013-03-14 | 2014-03-07 | Human antibodies to grem 1 |
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| CA2904644C true CA2904644C (en) | 2022-09-20 |
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| ES2720617T3 (es) * | 2012-03-15 | 2019-07-23 | Snu R&Db Foundation | Anticuerpo anti-gremlin-1 |
| KR20150129718A (ko) | 2013-03-14 | 2015-11-20 | 리제너론 파아마슈티컬스, 인크. | Ｇｒｅｍ 1에 대한 인간 항체 |
| SG11201808821WA (en) | 2016-04-18 | 2018-11-29 | Celldex Therapeutics Inc | Agonistic antibodies that bind human cd40 and uses thereof |
| CN106399316B (zh) * | 2016-08-26 | 2019-03-01 | 西安交通大学第一附属医院 | 用于识别Gremlin-1的核酸适配子及其应用 |
| JP2019529371A (ja) * | 2016-08-29 | 2019-10-17 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | 肺動脈性肺高血圧を処置するための抗グレムリン−１（ｇｒｅｍ１）抗体およびその使用の方法 |
| EP3554544A4 (en) | 2016-12-16 | 2020-07-29 | Bluefin Biomedicine, Inc. | ANTI-PROTEIN 1 ANTIBODY CONTAINING AN ANTI-CUB DOMAIN (CDCP1), ANTIBODY-DRUG CONJUGATES AND THEIR METHODS OF USE |
| GB201621635D0 (en) * | 2016-12-19 | 2017-02-01 | Ucb Biopharma Sprl | Crystal structure |
| WO2018175740A1 (en) * | 2017-03-22 | 2018-09-27 | Bluefin Biomedicine, Inc. | Anti-tmeff1 antibodies and antibody drug conjugates |
| WO2018175924A1 (en) * | 2017-03-24 | 2018-09-27 | The Broad Institute, Inc. | Methods and compositions for regulating innate lymphoid cell inflammatory responses |
| GB201802486D0 (en) * | 2018-02-15 | 2018-04-04 | Ucb Biopharma Sprl | Methods |
| AU2019289176A1 (en) | 2018-06-18 | 2020-12-24 | Oxford University Innovation Limited | Gremlin-1 antagonist for the prevention and treatment of cancer |
| WO2020106461A2 (en) * | 2018-11-08 | 2020-05-28 | Celldex Therapeutics, Inc. | Anti-mertk antibodies and methods of use thereof |
| CA3162181A1 (en) * | 2019-11-21 | 2021-05-27 | Unity Biotechnology | Antibodies directed to tie-2 and methods of use |
| EP4232475A1 (en) * | 2020-10-20 | 2023-08-30 | Kantonsspital St. Gallen | Antibodies or antigen-binding fragments specifically binding to gremlin-1 and uses thereof |
| WO2022150654A2 (en) * | 2021-01-08 | 2022-07-14 | 10X Genomics, Inc. | Antigen-binding polypeptides specific for coronaviruses and uses thereof |
| MX2023008423A (es) * | 2021-01-18 | 2023-07-26 | Suzhou Transcenta Therapeutics Co Ltd | Anticuerpos anti-gremlin1 novedosos. |
| GB202205200D0 (en) | 2022-04-08 | 2022-05-25 | Ucb Biopharma Sprl | Combination with chemotherapy |
| GB202205203D0 (en) | 2022-04-08 | 2022-05-25 | UCB Biopharma SRL | Combination with inhibitor |
| WO2023203177A1 (en) * | 2022-04-20 | 2023-10-26 | Kantonsspital St. Gallen | Antibodies or antigen-binding fragments pan-specifically binding to gremlin-1 and gremlin-2 and uses thereof |
| TW202409078A (zh) * | 2022-07-18 | 2024-03-01 | 中國大陸商蘇州創勝醫藥集團有限公司 | 穩定之包含抗gremlin1抗體的藥物製劑 |
| CN115786495A (zh) * | 2022-10-24 | 2023-03-14 | 杭州市第七人民医院 | 检测基因表达量的试剂在制备尼古丁加重的糖尿病肾病的筛查试剂盒中的用途 |
| AU2024255761A1 (en) * | 2023-04-13 | 2025-10-30 | Suzhou Transcenta Therapeutics Co., Ltd. | Combination therapies involving grem1 antagonists for treatment of cancer |
| CN117801109B (zh) * | 2024-03-01 | 2024-05-03 | 再少年(北京)生物科技有限公司 | iPS诱导定向分化成内皮祖细胞的方法及应用 |
Family Cites Families (23)
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|---|---|---|---|---|
| FR2437213A1 (fr) | 1978-09-28 | 1980-04-25 | Cm Ind | Produits cytotoxiques formes par liaison covalente de la chaine a de la ricine avec un anticorps et leur procede de preparation |
| AU6267098A (en) | 1997-02-05 | 1998-08-25 | Regents Of The University Of California, The | Morphogenic proteins |
| US7087411B2 (en) | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
| US6573096B1 (en) | 2000-04-01 | 2003-06-03 | The Research Foundation At State University Of New York | Compositions and methods for inhibition of cancer invasion and angiogenesis |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| EP1738767A1 (en) | 2001-10-31 | 2007-01-03 | Alcon, Inc. | Bone morphogenic proteins (BMP), BMP receptors and BMP binding proteins and their use in the diagnosis and treatment of glaucoma |
| MXPA04003697A (es) | 2001-10-31 | 2005-04-08 | Alcon Inc | Proteinas morfogenicas de hueso (bmp), receptores de bmp y proteinas de enlace de bmp y su uso en el diagnostico y tratamiento de glaucoma. |
| US20040101920A1 (en) | 2002-11-01 | 2004-05-27 | Czeslaw Radziejewski | Modification assisted profiling (MAP) methodology |
| JP5848861B2 (ja) | 2004-04-20 | 2016-01-27 | ジェンマブ エー／エスＧｅｎｍａｂ Ａ／Ｓ | Ｃｄ２０に対するヒトモノクローナル抗体 |
| US8257740B1 (en) | 2011-08-15 | 2012-09-04 | Gp Medical, Inc. | Pharmaceutical composition of nanoparticles |
| US20090041747A1 (en) | 2005-02-24 | 2009-02-12 | Novo Nordisk Health Care Ag | Compounds for Stabilizing Factor VII Polypeptide Formulations |
| US8246995B2 (en) | 2005-05-10 | 2012-08-21 | The Board Of Trustees Of The Leland Stanford Junior University | Hydrophobic nanotubes and nanoparticles as transporters for the delivery of drugs into cells |
| US7411046B2 (en) | 2005-08-02 | 2008-08-12 | Arius Research Inc | Cancerous disease modifying antibodies |
| WO2007081751A2 (en) | 2006-01-05 | 2007-07-19 | The Johns Hopkins University | Compositions and methods for the treatment of cancer |
| US7420040B2 (en) | 2006-02-24 | 2008-09-02 | Arius Research Inc. | Cytotoxicity mediation of cells evidencing surface expression of TROP-2 |
| US20090203041A1 (en) | 2006-04-21 | 2009-08-13 | Wei Shi | Bmp4 inhibitors |
| CN101454345B (zh) | 2006-06-02 | 2012-08-08 | 瑞泽恩制药公司 | 人il-6受体的高亲和力抗体 |
| US8383349B2 (en) | 2007-03-16 | 2013-02-26 | The Board Of Trustees Of The Leland Stanford Junior University | Bone morphogenetic protein antagonist and uses thereof |
| EA023175B1 (ru) | 2007-09-28 | 2016-05-31 | Бинд Терапьютикс, Инк. | Таргетирование раковых клеток с использованием наночастиц |
| US8277812B2 (en) | 2008-10-12 | 2012-10-02 | Massachusetts Institute Of Technology | Immunonanotherapeutics that provide IgG humoral response without T-cell antigen |
| WO2010151792A1 (en) | 2009-06-26 | 2010-12-29 | Regeneron Pharmaceuticals, Inc. | Readily isolated bispecific antibodies with native immunoglobulin format |
| ES2720617T3 (es) | 2012-03-15 | 2019-07-23 | Snu R&Db Foundation | Anticuerpo anti-gremlin-1 |
| KR20150129718A (ko) | 2013-03-14 | 2015-11-20 | 리제너론 파아마슈티컬스, 인크. | Ｇｒｅｍ 1에 대한 인간 항체 |
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| MX369574B (es) | 2019-11-13 |
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| JP2016519650A (ja) | 2016-07-07 |
| AU2014241442A1 (en) | 2015-10-15 |
| CA2904644A1 (en) | 2014-10-02 |
| US11634480B2 (en) | 2023-04-25 |
| EP2970448A1 (en) | 2016-01-20 |
| JP2019151654A (ja) | 2019-09-12 |
| ZA201506113B (en) | 2016-07-27 |
| US20200157194A1 (en) | 2020-05-21 |
| US20230192831A1 (en) | 2023-06-22 |
| CN105189548A (zh) | 2015-12-23 |
| EA201591762A1 (ru) | 2015-12-30 |
| US10377817B2 (en) | 2019-08-13 |
| CL2015002603A1 (es) | 2016-03-04 |
| SG11201506459PA (en) | 2015-09-29 |
| EP2970448B1 (en) | 2021-11-03 |
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