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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- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
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- A61P35/04—Antineoplastic agents specific for metastasis
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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
- C07K16/2896—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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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- 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
- C07K16/3076—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 against structure-related tumour-associated moieties
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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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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 |
Publications (2)
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| AU2015247358A1 AU2015247358A1 (en) | 2016-11-10 |
| AU2015247358B2 true AU2015247358B2 (en) | 2020-02-27 |
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| AU2015247358A Active AU2015247358B2 (en) | 2014-04-18 | 2015-04-20 | Humanized anti-TF-antigen antibodies |
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| US (1) | US11130821B2 (Direct) |
| EP (2) | EP3797793A1 (Direct) |
| JP (1) | JP6740135B2 (Direct) |
| KR (1) | KR102413809B1 (Direct) |
| CN (1) | CN106488774B (Direct) |
| AU (1) | AU2015247358B2 (Direct) |
| BR (1) | BR112016024214B8 (Direct) |
| ES (1) | ES2843546T3 (Direct) |
| MX (2) | MX378944B (Direct) |
| RU (1) | RU2699717C2 (Direct) |
| WO (1) | WO2015161311A2 (Direct) |
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| EP3609922A2 (en) * | 2017-04-13 | 2020-02-19 | Aduro Biotech Holdings, Europe B.V. | Anti-sirp alpha antibodies |
| WO2019060718A1 (en) * | 2017-09-22 | 2019-03-28 | Immunogen, Inc. | SEPARATION OF LIGHT TRIPLE CHAIN ANTIBODIES USING CATION EXCHANGE CHROMATOGRAPHY |
| US12060427B2 (en) * | 2018-03-28 | 2024-08-13 | Mitsubishi Tanabe Pharma Corporat | Drug conjugates of cMET monoclonal binding agents, and uses thereof |
| EP3801618A4 (en) * | 2018-05-30 | 2022-07-27 | National Health Research Institutes | Anti-abeta antibodies and uses thereof |
| BR112021012040A2 (pt) | 2018-12-21 | 2021-11-03 | Ose Immunotherapeutics | Molécula anti-pd-1/sirpa bifuncional |
| CA3123338A1 (en) | 2018-12-21 | 2020-06-25 | Ose Immunotherapeutics | Bifunctional anti-pd-1/il-7 molecule |
| BR112021012027A2 (pt) | 2018-12-21 | 2021-11-03 | Ose Immunotherapeutics | Molécula bifuncional direcionada contra pd-1 humano |
| JP7043685B2 (ja) | 2018-12-21 | 2022-03-29 | オーエスイー・イミュノセラピューティクス | ヒト化抗ヒトｐｄ－１抗体 |
| WO2020165374A1 (en) | 2019-02-14 | 2020-08-20 | Ose Immunotherapeutics | Bifunctional molecule comprising il-15ra |
| TW202202521A (zh) * | 2020-03-23 | 2022-01-16 | 美商必治妥美雅史谷比公司 | 用於治療癌症之抗ccr8抗體 |
| CN121270708A (zh) * | 2025-12-08 | 2026-01-06 | 宁波大学附属第一医院 | 一种纳米抗体及其在制备cd176阳性肿瘤癌症治疗或诊断药物中的应用 |
| CN121270707A (zh) * | 2025-12-08 | 2026-01-06 | 宁波大学附属第一医院 | 一种特异性结合cd176蛋白的纳米抗体及其应用 |
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 |
| KR20080113236A (ko) | 2006-03-21 | 2008-12-29 | 와이어쓰 | Ｒａｇｅ를 길항하기 위한 방법 및 조성물 |
| EP2161031A1 (en) * | 2008-09-05 | 2010-03-10 | SuppreMol GmbH | Fc gamma receptor for the treatment of B cell mediated multiple sclerosis |
| MX351635B (es) * | 2009-10-16 | 2017-10-23 | Servier Lab | Anticuerpos monoclonales frente a progastrina y sus usos. |
| 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 |
| WO2012143524A2 (en) | 2011-04-20 | 2012-10-26 | Genmab A/S | Bispecific antibodies against her2 and cd3 |
| JP6124800B2 (ja) * | 2011-11-30 | 2017-05-10 | 中外製薬株式会社 | 免疫複合体を形成する細胞内への運搬体（キャリア）を含む医薬 |
| 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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| CA2943681A1 (en) | 2015-10-22 |
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| KR102413809B1 (ko) | 2022-06-28 |
| EP3131581B1 (en) | 2020-09-23 |
| BR112016024214B1 (pt) | 2023-11-14 |
| JP2017518260A (ja) | 2017-07-06 |
| US11130821B2 (en) | 2021-09-28 |
| WO2015161311A2 (en) | 2015-10-22 |
| BR112016024214A2 (pt) | 2018-01-23 |
| AU2015247358A1 (en) | 2016-11-10 |
| RU2016143552A (ru) | 2018-05-21 |
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