JP7155126B2 - ヒトｉｌ－１５に特異的に結合する抗体及びその使用 - Google Patents
ヒトｉｌ－１５に特異的に結合する抗体及びその使用 Download PDFInfo
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| DK3558369T3 (da) | 2016-12-21 | 2025-05-19 | Cephalon Llc | Antistoffer, der specifikt binder til humant il-15, og anvendelse heraf |
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| WO2018231864A1 (en) | 2017-06-12 | 2018-12-20 | Twist Bioscience Corporation | Methods for seamless nucleic acid assembly |
| JP2020536504A (ja) | 2017-09-11 | 2020-12-17 | ツイスト バイオサイエンス コーポレーション | Ｇｐｃｒ結合タンパク質およびその合成 |
| KR102889470B1 (ko) | 2017-10-20 | 2025-11-21 | 트위스트 바이오사이언스 코포레이션 | 폴리뉴클레오타이드 합성을 위한 가열된 나노웰 |
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| CA3100739A1 (en) | 2018-05-18 | 2019-11-21 | Twist Bioscience Corporation | Polynucleotides, reagents, and methods for nucleic acid hybridization |
| WO2020023702A1 (en) | 2018-07-25 | 2020-01-30 | AskGene Pharma, Inc. | Novel il-21 prodrugs and methods of use thereof |
| WO2020138073A1 (ja) | 2018-12-25 | 2020-07-02 | Ntn株式会社 | 流量制御バルブ用シールおよび流量制御バルブ装置 |
| CN119708086A (zh) | 2018-12-26 | 2025-03-28 | 特韦斯特生物科学公司 | 高度准确的从头多核苷酸合成 |
| EP3930753A4 (en) | 2019-02-26 | 2023-03-29 | Twist Bioscience Corporation | VARIANT NUCLEIC ACID LIBRARIES FOR GLP1 RECEPTOR |
| AU2020227802A1 (en) | 2019-02-26 | 2021-10-14 | Twist Bioscience Corporation | Variant nucleic acid libraries for antibody optimization |
| US11845801B2 (en) | 2019-06-12 | 2023-12-19 | AskGene Pharma, Inc. | IL-15 prodrugs and methods of use thereof |
| CN114729342A (zh) | 2019-06-21 | 2022-07-08 | 特韦斯特生物科学公司 | 基于条形码的核酸序列装配 |
| WO2021061829A1 (en) | 2019-09-23 | 2021-04-01 | Twist Bioscience Corporation | Variant nucleic acid libraries for crth2 |
| AU2020355027A1 (en) | 2019-09-23 | 2022-04-21 | Twist Bioscience Corporation | Antibodies that bind CD3 Epsilon |
| IL293670A (en) * | 2019-12-09 | 2022-08-01 | Twist Bioscience Corp | Variant nucleic acid libraries for adenosine receptors |
| CN116391127A (zh) * | 2020-10-16 | 2023-07-04 | 基因泰克公司 | 抗切割icaspase底物抗体及其使用方法 |
| CA3206018A1 (en) | 2021-01-21 | 2022-07-28 | Twist Bioscience Corporation | Methods and compositions relating to adenosine receptors |
| CN113185600A (zh) * | 2021-05-28 | 2021-07-30 | 苏州复融生物技术有限公司 | 一种新型白介素15突变体多肽的开发及其应用 |
| JP2025525860A (ja) | 2022-08-04 | 2025-08-07 | ノバルティス ファーマ アーゲー | アトピー性皮膚炎の治療に有用なｉｌ－１５阻害剤 |
| CN118894934A (zh) * | 2023-05-05 | 2024-11-05 | 北京智仁美博生物科技有限公司 | 抗人il-15的抗体及其用途 |
| CN117209605B (zh) * | 2023-11-09 | 2024-01-30 | 北京百普赛斯生物科技股份有限公司 | 特异性结合il-15的抗体及其应用 |
| WO2025227052A1 (en) | 2024-04-26 | 2025-10-30 | Cephalon Llc | Doses and formulations of anti-il-15 antibody for the treatment of immune diseases |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008133276A (ja) | 1995-02-22 | 2008-06-12 | Immunex Corp | インターロイキン−１５のアンタゴニスト |
| WO2016001275A1 (en) | 2014-07-02 | 2016-01-07 | Calypso Biotech Sa | Antibodies to il-15 |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101155191B1 (ko) | 1999-01-15 | 2012-06-13 | 제넨테크, 인크. | 효과기 기능이 변화된 폴리펩티드 변이체 |
| DK1355919T3 (da) | 2000-12-12 | 2011-03-14 | Medimmune Llc | Molekyler med længere halveringstider, sammensætninger og anvendelser deraf |
| US7132510B2 (en) | 2000-12-29 | 2006-11-07 | Bio-Technology General (Israel) Ltd. | Specific human antibodies for selective cancer therapy |
| NZ531211A (en) * | 2001-08-23 | 2007-04-27 | Genmad As | Human antibodies specific for interleukin 15 (IL-15) |
| US7247304B2 (en) * | 2001-08-23 | 2007-07-24 | Genmab A/S | Methods of treating using anti-IL-15 antibodies |
| US7329405B2 (en) * | 2001-08-23 | 2008-02-12 | Genmab A/S | Human antibodies specific for interleukin 15 (IL-15) |
| US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| US7217797B2 (en) | 2002-10-15 | 2007-05-15 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
| US7285269B2 (en) * | 2002-12-02 | 2007-10-23 | Amgen Fremont, Inc. | Antibodies directed to tumor necrosis factor |
| EA015897B1 (ru) * | 2003-02-26 | 2011-12-30 | Генмаб А/С | Применение человеческого моноклонального антитела к ил-15 в составе композиции и лекарственного препарата (варианты), композиция и лекарственный препарат, его включающие |
| US20060057102A1 (en) * | 2004-08-11 | 2006-03-16 | Zheng Xin X | Mutant interleukin-15-containing compositions and suppression of an immune response |
| JP4942644B2 (ja) | 2005-02-28 | 2012-05-30 | 株式会社抗体研究所 | 抗ＩｇＳＦ４抗体及びその利用 |
| DK2161336T4 (en) * | 2005-05-09 | 2017-04-24 | Ono Pharmaceutical Co | Human monoclonal antibodies for programmed death 1 (PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapies |
| PT2336329E (pt) | 2007-06-01 | 2012-12-24 | Omt Inc | Composições e métodos para inibição de genes de imunoglobulina endógena e produção de anticorpos transgénicos humanos idiotípicos |
| TWI489993B (zh) * | 2007-10-12 | 2015-07-01 | Novartis Ag | 骨硬化素（ｓｃｌｅｒｏｓｔｉｎ）抗體組合物及使用方法 |
| PT2564695E (pt) * | 2009-07-08 | 2015-06-03 | Kymab Ltd | Modelos animais e moléculas terapêuticas |
| KR20120104542A (ko) * | 2009-10-15 | 2012-09-21 | 아보트 러보러터리즈 | Ｉｌ?１ 결합 단백질 |
| WO2011119484A1 (en) * | 2010-03-23 | 2011-09-29 | Iogenetics, Llc | Bioinformatic processes for determination of peptide binding |
| WO2012009760A1 (en) | 2010-07-20 | 2012-01-26 | Cephalon Australia Pty Ltd | Anti-il-23 heterodimer specific antibodies |
| JP5820688B2 (ja) | 2011-03-23 | 2015-11-24 | 株式会社Kri | 多糖類の溶解に用いられる溶媒ならびに該溶媒を用いた成形体および多糖類誘導体の製造方法 |
| KR20140048292A (ko) * | 2011-08-23 | 2014-04-23 | 로슈 글리카트 아게 | 항-mcsp 항체 |
| WO2013059885A2 (en) * | 2011-10-28 | 2013-05-02 | Cephalon Australia Pty Ltd | Polypeptide constructs and uses thereof |
| CN105143270B (zh) | 2013-02-26 | 2019-11-12 | 罗切格利卡特公司 | 双特异性t细胞活化抗原结合分子 |
| UA118028C2 (uk) | 2013-04-03 | 2018-11-12 | Рош Глікарт Аг | Біспецифічне антитіло, специфічне щодо fap і dr5, антитіло, специфічне щодо dr5, і спосіб їх застосування |
| ES2886114T3 (es) | 2015-03-31 | 2021-12-16 | Medimmune Ltd | Una nueva forma de IL33, formas mutadas de IL33, anticuerpos, ensayos y métodos para usar los mismos |
| EP3472202A1 (en) | 2016-06-15 | 2019-04-24 | Amgen Inc. | Methods and compositions for the treatment of celiac disease, non-celiac gluten sensitivity, and refractory celiac disease |
| SG11201903302UA (en) | 2016-10-14 | 2019-05-30 | Xencor Inc | Bispecific heterodimeric fusion proteins containing il-15/il-15ralpha fc-fusion proteins and pd-1 antibody fragments |
| DK3558369T3 (da) | 2016-12-21 | 2025-05-19 | Cephalon Llc | Antistoffer, der specifikt binder til humant il-15, og anvendelse heraf |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008133276A (ja) | 1995-02-22 | 2008-06-12 | Immunex Corp | インターロイキン−１５のアンタゴニスト |
| WO2016001275A1 (en) | 2014-07-02 | 2016-01-07 | Calypso Biotech Sa | Antibodies to il-15 |
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