JP6644678B2 - Ｃｔｌａ−４およびｃｄ４０の両方に特異的に結合可能である二重特異性分子 - Google Patents
Ｃｔｌａ−４およびｃｄ４０の両方に特異的に結合可能である二重特異性分子 Download PDFInfo
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- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- 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
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
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- C—CHEMISTRY; METALLURGY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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| GB1311487.1 | 2013-06-27 | ||
| GB201311487A GB201311487D0 (en) | 2013-06-27 | 2013-06-27 | Bispecific molecules |
| PCT/EP2014/063443 WO2014207064A1 (en) | 2013-06-27 | 2014-06-25 | Bispecific molecules capable of specifically binding to both ctla-4 and cd40 |
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| JP2016529215A JP2016529215A (ja) | 2016-09-23 |
| JP2016529215A5 JP2016529215A5 (OSRAM) | 2017-08-03 |
| JP6644678B2 true JP6644678B2 (ja) | 2020-02-12 |
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| JP (1) | JP6644678B2 (OSRAM) |
| GB (1) | GB201311487D0 (OSRAM) |
| WO (1) | WO2014207064A1 (OSRAM) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12466897B2 (en) | 2011-10-10 | 2025-11-11 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
| US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
| CA2898100C (en) | 2013-01-14 | 2023-10-10 | Xencor, Inc. | Novel heterodimeric proteins |
| US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| GB201322583D0 (en) * | 2013-12-19 | 2014-02-05 | Alligator Bioscience Ab | Antibodies |
| MX385936B (es) | 2014-03-28 | 2025-03-11 | Xencor Inc | Anticuerpos biespecíficos que se unen a cd38 y cd3. |
| WO2015153912A1 (en) | 2014-04-03 | 2015-10-08 | Igm Biosciences, Inc. | Modified j-chain |
| CA2961950A1 (en) | 2014-09-28 | 2016-03-31 | The Regents Of The University Of California | Modulation of stimulatory and non-stimulatory myeloid cells |
| US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
| HRP20211273T1 (hr) | 2014-11-26 | 2021-11-12 | Xencor, Inc. | Heterodimerna protutijela koja vežu cd3 i cd20 |
| MX2017006918A (es) | 2014-11-26 | 2018-01-25 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y cd38. |
| KR20240135877A (ko) | 2015-03-04 | 2024-09-12 | 아이쥐엠 바이오사이언스 인코포레이티드 | Ｃｄ20 결합 분자 및 그의 용도 |
| CN107709367A (zh) * | 2015-05-21 | 2018-02-16 | 鳄鱼生物科学公司 | 新型多肽 |
| CN107949573B (zh) | 2015-09-01 | 2022-05-03 | 艾吉纳斯公司 | 抗-pd-1抗体及其使用方法 |
| DK3356401T3 (da) * | 2015-09-30 | 2020-09-07 | Igm Biosciences Inc | Bindingsmolekyler med modificeret j-kæde |
| HK1252791A1 (zh) | 2015-09-30 | 2019-06-06 | Igm Biosciences, Inc. | 具有经修饰的j链的结合分子 |
| JP7058219B2 (ja) | 2015-12-07 | 2022-04-21 | ゼンコア インコーポレイテッド | Ｃｄ３及びｐｓｍａに結合するヘテロ二量体抗体 |
| FI3468586T3 (fi) | 2016-06-14 | 2024-10-29 | Xencor Inc | Bispesifisiä immuuniaktivaatiota vapauttavia vasta-aineita |
| EP3475304B1 (en) | 2016-06-28 | 2022-03-23 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
| US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| WO2018045110A1 (en) * | 2016-08-30 | 2018-03-08 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| KR102576042B1 (ko) | 2016-10-11 | 2023-09-07 | 아게누스 인코포레이티드 | 항-lag-3 항체 및 이의 사용 방법 |
| TWI788307B (zh) * | 2016-10-31 | 2023-01-01 | 美商艾歐凡斯生物治療公司 | 用於擴增腫瘤浸潤性淋巴細胞之工程化人造抗原呈現細胞 |
| PE20200006A1 (es) | 2017-04-04 | 2020-01-06 | Hoffmann La Roche | Nuevas moleculas de union antigeno biespecificas capaces de unirse especificamente cd40 y a fap |
| WO2019094637A1 (en) | 2017-11-08 | 2019-05-16 | Xencor, Inc. | Bispecific and monospecific antibodies using novel anti-pd-1 sequences |
| EP3708589A4 (en) * | 2017-11-08 | 2021-08-11 | Kyowa Kirin Co., Ltd. | BISPECIFIC ANTIBODIES THAT BIND TO CD40 AND EpCAM |
| US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| KR102860409B1 (ko) | 2017-12-12 | 2025-09-16 | 파이오니어 임뮤노테라퓨틱스, 인코퍼레이티드 | 항-trem2 항체 및 관련 방법 |
| KR102722731B1 (ko) | 2017-12-19 | 2024-10-25 | 젠코어 인코포레이티드 | 조작된 il-2 fc 융합 단백질 |
| CN118852460A (zh) * | 2017-12-28 | 2024-10-29 | 尤利乌斯·马克西米利安维尔茨堡大学 | 具有非FcγR依赖性激动活性的肿瘤坏死因子(TNF)受体超家族(TNFRSF)受体-激活抗体融合蛋白(具有非FcγR依赖性激动活性的TNFRSF受体-激活抗体融合蛋白；TRAAFFIAA) |
| CN112469477A (zh) | 2018-04-04 | 2021-03-09 | Xencor股份有限公司 | 与成纤维细胞活化蛋白结合的异源二聚体抗体 |
| JP2021521784A (ja) | 2018-04-18 | 2021-08-30 | ゼンコア インコーポレイテッド | ＩＬ−１５／ＩＬ−１５ＲａＦｃ融合タンパク質とＰＤ−１抗原結合ドメインを含むＰＤ−１標的化ヘテロダイマー融合タンパク質およびそれらの使用 |
| CA3097741A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains |
| CN112638375A (zh) | 2018-06-15 | 2021-04-09 | 旗舰创业创新五公司 | 通过后细胞信号传导因子的调节来增加免疫活性 |
| SG11202103192RA (en) | 2018-10-03 | 2021-04-29 | Xencor Inc | Il-12 heterodimeric fc-fusion proteins |
| CA3120875A1 (en) * | 2018-12-11 | 2020-06-18 | Pionyr Immunotherapeutics, Inc. | Methods of using anti-trem2 antibodies |
| MX2021010390A (es) | 2019-03-01 | 2021-11-17 | Xencor Inc | Anticuerpos heterodimericos que se unen a enpp3 y cd3. |
| EP3962493A2 (en) | 2019-05-03 | 2022-03-09 | Flagship Pioneering Innovations V, Inc. | Methods of modulating immune activity/level of irf or sting or of treating cancer, comprising the administration of a sting modulator and/or purinergic receptor modulator or postcellular signaling factor |
| WO2021127217A1 (en) | 2019-12-17 | 2021-06-24 | Flagship Pioneering Innovations V, Inc. | Combination anti-cancer therapies with inducers of iron-dependent cellular disassembly |
| WO2021231976A1 (en) | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3 |
| EP4172323A1 (en) | 2020-06-29 | 2023-05-03 | Flagship Pioneering Innovations V, Inc. | Viruses engineered to promote thanotransmission and their use in treating cancer |
| WO2022040482A1 (en) | 2020-08-19 | 2022-02-24 | Xencor, Inc. | Anti-cd28 and/or anti-b7h3 compositions |
| CN117157319A (zh) | 2021-03-09 | 2023-12-01 | Xencor股份有限公司 | 结合cd3和cldn6的异二聚抗体 |
| KR20230154311A (ko) | 2021-03-10 | 2023-11-07 | 젠코어 인코포레이티드 | Cd3 및 gpc3에 결합하는 이종이량체 항체 |
| KR20230165276A (ko) | 2021-03-31 | 2023-12-05 | 플래그쉽 파이어니어링 이노베이션스 브이, 인크. | 타노트랜스미션 폴리펩티드 및 암의 치료에서의 이의 용도 |
| AU2022303363A1 (en) | 2021-06-29 | 2024-01-18 | Flagship Pioneering Innovations V, Inc. | Immune cells engineered to promote thanotransmission and uses thereof |
| US20240174732A1 (en) | 2022-10-05 | 2024-05-30 | Flagship Pioneering Innovations V, Inc. | Nucleic acid molecules encoding trif and additional polypeptides and their use in treating cancer |
| US20240269251A1 (en) | 2023-01-09 | 2024-08-15 | Flagship Pioneering Innovations V, Inc. | Genetic switches and their use in treating cancer |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EE05627B1 (et) | 1998-12-23 | 2013-02-15 | Pfizer Inc. | CTLA-4 vastased inimese monoklonaalsed antikehad |
| JP4430303B2 (ja) | 2000-12-12 | 2010-03-10 | アリゲーター・バイオサイエンス・アーベー | タンパク質機能のインビトロ分子進化方法 |
| US6618871B2 (en) | 2001-07-24 | 2003-09-16 | Kohler Co. | Shower door assembly |
| AR039067A1 (es) * | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
| GB2432366B (en) | 2005-11-19 | 2007-11-21 | Alligator Bioscience Ab | A method for in vitro molecular evolution of protein function |
| EP2475682B1 (en) * | 2009-09-10 | 2018-01-31 | UCB Biopharma SPRL | Multivalent antibodies |
| GB0920258D0 (en) * | 2009-11-19 | 2010-01-06 | Alligator Bioscience Ab | New medical agents and use thereof |
| AU2011235214B2 (en) * | 2010-03-31 | 2015-04-23 | Boehringer Ingelheim International Gmbh | Anti-CD40 antibodies |
| DK2663580T3 (en) * | 2011-01-10 | 2017-03-13 | Ct Atlantic Ltd | COMBINATION THERAPY INCLUDING TUMOR ASSOCIATED ANTI-BINDING ANTIBODIES |
| JP6130307B2 (ja) * | 2011-03-17 | 2017-05-17 | ザ ユニバーシティ オブ バーミンガム | 再指向性免疫療法 |
| BR112013033661A2 (pt) * | 2011-06-30 | 2017-01-24 | Genzyme Corp | inibidores de ativação de células t |
| WO2013043569A1 (en) * | 2011-09-20 | 2013-03-28 | Vical Incorporated | Synergistic anti-tumor efficacy using alloantigen combination immunotherapy |
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- 2014-06-25 US US14/901,222 patent/US20170304437A1/en not_active Abandoned
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| US20170304437A1 (en) | 2017-10-26 |
| GB201311487D0 (en) | 2013-08-14 |
| EP3013859B1 (en) | 2018-05-30 |
| EP3013859A1 (en) | 2016-05-04 |
| WO2014207064A1 (en) | 2014-12-31 |
| JP2016529215A (ja) | 2016-09-23 |
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