AU2015247358B2 - Humanized anti-TF-antigen antibodies - Google Patents
Humanized anti-TF-antigen antibodies Download PDFInfo
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- AU2015247358B2 AU2015247358B2 AU2015247358A AU2015247358A AU2015247358B2 AU 2015247358 B2 AU2015247358 B2 AU 2015247358B2 AU 2015247358 A AU2015247358 A AU 2015247358A AU 2015247358 A AU2015247358 A AU 2015247358A AU 2015247358 B2 AU2015247358 B2 AU 2015247358B2
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- 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
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Landscapes
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| US201461981240P | 2014-04-18 | 2014-04-18 | |
| US61/981,240 | 2014-04-18 | ||
| PCT/US2015/026595 WO2015161311A2 (en) | 2014-04-18 | 2015-04-20 | Humanized anti-tf-antigen antibodies |
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| AU2015247358A1 AU2015247358A1 (en) | 2016-11-10 |
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| SG11201908813QA (en) * | 2017-04-13 | 2019-10-30 | Aduro Biotech Holdings Europe B V | Anti-sirp alpha antibodies |
| TWI826393B (zh) * | 2017-09-22 | 2023-12-21 | 美商免疫遺傳股份有限公司 | 使用陽離子交換層析法分離三輕鏈抗體 |
| SG11202009308WA (en) * | 2018-03-28 | 2020-10-29 | Mitsubishi Tanabe Pharma Corp | DRUG CONJUGATES OF cMET MONOCLONAL BINDING AGENTS, AND USES THEREOF |
| WO2019231957A1 (en) * | 2018-05-30 | 2019-12-05 | National Health Research Institutes | Anti-abeta antibodies and uses thereof |
| CA3122899A1 (en) | 2018-12-21 | 2020-06-25 | Ose Immunotherapeutics | Bifunctional molecule directed against human pd-1 |
| KR20210107062A (ko) | 2018-12-21 | 2021-08-31 | 오제 이뮈노테라프틱스 | 이작용성 항-PD-1/SIRPα 분자 |
| BR112021011982A2 (pt) | 2018-12-21 | 2021-09-14 | Ose Immunotherapeutics | Anticorpo anti-humano-pd-1 humanizado |
| CA3123338A1 (en) | 2018-12-21 | 2020-06-25 | Ose Immunotherapeutics | Bifunctional anti-pd-1/il-7 molecule |
| WO2020165374A1 (en) | 2019-02-14 | 2020-08-20 | Ose Immunotherapeutics | Bifunctional molecule comprising il-15ra |
| CA3172697A1 (en) * | 2020-03-23 | 2021-09-30 | Ruth Yin-Zong LAN | Anti-ccr8 antibodies for treating cancer |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050260680A1 (en) * | 2004-04-16 | 2005-11-24 | Vanderbilt University | Methods of diagnosing and treating autoimmune diseases |
| US20060018913A1 (en) * | 2004-07-26 | 2006-01-26 | Kate Rittenhouse-Olson | Therapeutic use of anti-TF-Antigen antibody |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0510790D0 (en) * | 2005-05-26 | 2005-06-29 | Syngenta Crop Protection Ag | Anti-CD16 binding molecules |
| AU2007226863A1 (en) * | 2006-03-21 | 2007-09-27 | Wyeth | Methods for preventing and treating amyloidogenic diseases |
| EP2161031A1 (en) * | 2008-09-05 | 2010-03-10 | SuppreMol GmbH | Fc gamma receptor for the treatment of B cell mediated multiple sclerosis |
| PL2488551T3 (pl) * | 2009-10-16 | 2019-01-31 | Progastrine Et Cancers S.À R.L. | Przeciwciała monoklonalne przeciwko progastrynie i ich zastosowania |
| EP2347769A1 (en) * | 2010-01-20 | 2011-07-27 | Glycotope GmbH | Cancer stem cell markers and uses thereof |
| EP2407487A1 (en) * | 2010-07-14 | 2012-01-18 | F-Star Biotechnologische Forschungs - und Entwicklungsges. M.B.H. | Multispecific modular antibody |
| JP2014514314A (ja) * | 2011-04-20 | 2014-06-19 | ゲンマブ エー／エス | Ｈｅｒ２およびｃｄ３に対する二重特異性抗体 |
| BR112014013081A2 (pt) * | 2011-11-30 | 2020-10-20 | Chugai Seiyaku Kabushiki Kaisha | veículo contendo fármaco em célula para formação de um complexo imune |
| CN102796144A (zh) * | 2012-08-22 | 2012-11-28 | 山东大学 | Tf抗原及其类似物、和其化学酶法合成方法及其应用 |
| US10023651B2 (en) * | 2014-04-18 | 2018-07-17 | The Research Foundation For The State University Of New York | Humanized anti-TF-antigen antibodies |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050260680A1 (en) * | 2004-04-16 | 2005-11-24 | Vanderbilt University | Methods of diagnosing and treating autoimmune diseases |
| US20060018913A1 (en) * | 2004-07-26 | 2006-01-26 | Kate Rittenhouse-Olson | Therapeutic use of anti-TF-Antigen antibody |
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| EP3131581A2 (en) | 2017-02-22 |
| CA2943681A1 (en) | 2015-10-22 |
| BR112016024214B8 (pt) | 2023-12-26 |
| BR112016024214B1 (pt) | 2023-11-14 |
| KR102413809B1 (ko) | 2022-06-28 |
| AU2015247358A1 (en) | 2016-11-10 |
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| EP3131581B1 (en) | 2020-09-23 |
| RU2016143552A (ru) | 2018-05-21 |
| CN106488774A (zh) | 2017-03-08 |
| CN106488774B (zh) | 2019-11-01 |
| WO2015161311A3 (en) | 2015-12-10 |
| RU2016143552A3 (enExample) | 2018-11-14 |
| BR112016024214A2 (pt) | 2018-01-23 |
| ES2843546T3 (es) | 2021-07-19 |
| MX2021000439A (es) | 2021-03-25 |
| JP2017518260A (ja) | 2017-07-06 |
| WO2015161311A2 (en) | 2015-10-22 |
| RU2699717C2 (ru) | 2019-09-09 |
| EP3131581A4 (en) | 2018-02-21 |
| KR20170010356A (ko) | 2017-01-31 |
| JP6740135B2 (ja) | 2020-08-12 |
| MX378944B (es) | 2025-03-10 |
| US11130821B2 (en) | 2021-09-28 |
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