NZ528265A - Screening of compounds which modulate PD-1 signalling by testing for compounds that modulate phosphorylation of SHP-2, ERK1 or ERK-2, and PKC-theta - Google Patents
Screening of compounds which modulate PD-1 signalling by testing for compounds that modulate phosphorylation of SHP-2, ERK1 or ERK-2, and PKC-theta Download PDFInfo
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- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Investigating Or Analysing Biological Materials (AREA)
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| US6803192B1 (en) * | 1999-11-30 | 2004-10-12 | Mayo Foundation For Medical Education And Research | B7-H1, a novel immunoregulatory molecule |
| US7030219B2 (en) | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
| EP2388590A1 (en) * | 2001-04-02 | 2011-11-23 | Dana Farber Cancer Institute | PD-1, a receptor for B7-4, and uses thereof |
| AU2002258941A1 (en) * | 2001-04-20 | 2002-11-05 | Mayo Foundation For Medical Education And Research | Methods of enhancing cell responsiveness |
| EP1389209B1 (en) * | 2001-04-24 | 2009-04-08 | Purdue Research Foundation | Folate mimetics and folate-receptor binding conjugates thereof |
| ES2324708T3 (es) * | 2002-05-15 | 2009-08-13 | Endocyte, Inc. | Conjugados de vitamina-mitomicina. |
| EP1537878B1 (en) | 2002-07-03 | 2010-09-22 | Ono Pharmaceutical Co., Ltd. | Immunopotentiating compositions |
| US7052694B2 (en) * | 2002-07-16 | 2006-05-30 | Mayo Foundation For Medical Education And Research | Dendritic cell potentiation |
| US7432351B1 (en) | 2002-10-04 | 2008-10-07 | Mayo Foundation For Medical Education And Research | B7-H1 variants |
| US7449300B2 (en) * | 2002-11-21 | 2008-11-11 | Mayo Foundation For Medical Education And Research | Detection of antibodies specific for B7-H1 in subjects with diseases or pathological conditions mediated by activated T cells |
| EP1592457B1 (en) | 2003-01-27 | 2012-07-25 | Endocyte, Inc. | Folate-vinblastine conjugate as medicament |
| US7501119B2 (en) * | 2004-06-30 | 2009-03-10 | Mayo Foundation For Medical Education And Research | Methods and molecules for modulating an immune response |
| US20060099203A1 (en) | 2004-11-05 | 2006-05-11 | Pease Larry R | B7-DC binding antibody |
| US8288557B2 (en) * | 2004-07-23 | 2012-10-16 | Endocyte, Inc. | Bivalent linkers and conjugates thereof |
| PL3428191T3 (pl) | 2004-10-06 | 2025-04-07 | Mayo Foundation For Medical Education And Research | B7-H1 i PD-1 w leczeniu raka nerkowokomórkowego |
| CN101175757B (zh) * | 2005-03-16 | 2012-11-14 | 恩多塞特公司 | 蝶酸及其缀合物的合成和纯化 |
| AU2011203119C1 (en) * | 2005-05-09 | 2018-06-14 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
| EP2418278A3 (en) | 2005-05-09 | 2012-07-04 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
| DK1907000T4 (da) | 2005-06-08 | 2020-03-30 | The President And Fellows Of Harvard College | Fremgangsmåder og sammensætninger til behandling af persisterende HIV-infektioner ved hæmning af reaktionsvejen for programmeret celledød 1 (PD-1). |
| KR101607288B1 (ko) | 2005-07-01 | 2016-04-05 | 이. 알. 스퀴부 앤드 선즈, 엘.엘.씨. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날 항체 |
| CN103893779A (zh) * | 2005-08-19 | 2014-07-02 | 恩多塞特公司 | 多药物配体缀合物 |
| EP1948240A2 (en) * | 2005-08-19 | 2008-07-30 | Endocyte, Inc. | Ligand conjugates of vinca alkaloids, analogs and derivatives |
| JP5093097B2 (ja) | 2006-03-03 | 2012-12-05 | 小野薬品工業株式会社 | 細胞表面機能分子の細胞外領域多量体 |
| AU2007342338A1 (en) * | 2006-09-20 | 2008-07-17 | The Johns Hopkins University | Combinatorial therapy of cancer and infectious diseases with anti-B7-H1 antibodies |
| CA2947292C (en) * | 2006-12-27 | 2019-07-23 | Emory University | Compositions and methods for the treatment of infections and tumors |
| AU2013200388B2 (en) * | 2006-12-27 | 2014-10-23 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for the treatment of infections and tumors |
| US20100104626A1 (en) * | 2007-02-16 | 2010-04-29 | Endocyte, Inc. | Methods and compositions for treating and diagnosing kidney disease |
| CN101678124A (zh) * | 2007-03-14 | 2010-03-24 | 恩多塞特公司 | 结合配体连接的微管溶素递药缀合物 |
| EP2535354B1 (en) | 2007-06-18 | 2017-01-11 | Merck Sharp & Dohme B.V. | Antibodies to human programmed death receptor pd-1 |
| CN104383553A (zh) | 2007-06-25 | 2015-03-04 | 恩多塞特公司 | 含有亲水性间隔区接头的共轭物 |
| US9877965B2 (en) | 2007-06-25 | 2018-01-30 | Endocyte, Inc. | Vitamin receptor drug delivery conjugates for treating inflammation |
| AU2008316835B2 (en) | 2007-10-25 | 2015-07-16 | Endocyte, Inc. | Tubulysins and processes for preparing |
| US8647822B2 (en) | 2007-11-28 | 2014-02-11 | Oregon Health & Science University | Determining whether a test compound modulates PD-1 activity in activated immune cells using gene expression profiles |
| EA023148B1 (ru) | 2008-08-25 | 2016-04-29 | Эмплиммьюн, Инк. | Композиции на основе антагонистов pd-1 и их применение |
| HUE030807T2 (en) | 2008-09-26 | 2017-05-29 | Dana Farber Cancer Inst Inc | Human anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies and their applications |
| JP5520961B2 (ja) | 2008-11-28 | 2014-06-11 | エモリー ユニバーシティ | 感染症および腫瘍を処置するための方法 |
| TWI729512B (zh) | 2008-12-09 | 2021-06-01 | 美商建南德克公司 | 抗pd-l1抗體及其於增進t細胞功能之用途 |
| WO2010104617A2 (en) | 2009-01-23 | 2010-09-16 | Salvatore Albani | Novel methods to induce a state of immune tolerance |
| EP2482849B1 (en) | 2009-09-30 | 2018-06-06 | Memorial Sloan-Kettering Cancer Center | Combination immunotherapy for the treatment of cancer |
| CA2790134A1 (en) * | 2010-02-16 | 2011-08-25 | Valorisation-Recherche, Limited Partnership | Pd-1 modulation and uses thereof for modulating hiv replication |
| CN102892786B (zh) | 2010-03-11 | 2016-03-16 | Ucb医药有限公司 | Pd-1抗体 |
| TW201134488A (en) * | 2010-03-11 | 2011-10-16 | Ucb Pharma Sa | PD-1 antibodies |
| US9783578B2 (en) | 2010-06-25 | 2017-10-10 | Aurigene Discovery Technologies Limited | Immunosuppression modulating compounds |
| US8907053B2 (en) | 2010-06-25 | 2014-12-09 | Aurigene Discovery Technologies Limited | Immunosuppression modulating compounds |
| GB201103631D0 (en) * | 2011-03-03 | 2011-04-13 | Univ Leeds | Identification of candidate therapeutics |
| WO2012168944A1 (en) | 2011-06-08 | 2012-12-13 | Aurigene Discovery Technologies Limited | Therapeutic compounds for immunomodulation |
| LT2768524T (lt) * | 2011-10-17 | 2022-07-25 | Io Biotech Aps | Pd-l1 grindžiama imunoterapija |
| US10080805B2 (en) | 2012-02-24 | 2018-09-25 | Purdue Research Foundation | Cholecystokinin B receptor targeting for imaging and therapy |
| CN104159911A (zh) | 2012-03-07 | 2014-11-19 | 奥瑞基尼探索技术有限公司 | 作为免疫调节剂的模拟肽化合物 |
| US20140080175A1 (en) | 2012-03-29 | 2014-03-20 | Endocyte, Inc. | Processes for preparing tubulysin derivatives and conjugates thereof |
| RU2014143443A (ru) | 2012-03-29 | 2016-05-20 | Ориджин Дискавери Текнолоджиз Лимитед | Иммуномодулирующие циклические соединения |
| KR102702287B1 (ko) | 2012-05-15 | 2024-09-04 | 브리스톨-마이어스 스큅 컴퍼니 | Pd-1/pd-l1 신호전달을 방해하는 것에 의한 암 면역요법 |
| WO2013177102A2 (en) * | 2012-05-21 | 2013-11-28 | Felder Mitchell S | Treatment of cancer by manipulating the immune system |
| EP2890715B1 (en) * | 2012-08-03 | 2020-12-16 | Dana-Farber Cancer Institute, Inc. | Single agent anti-pd-l1 and pd-l2 dual binding antibodies and methods of use |
| US9562892B2 (en) | 2012-10-02 | 2017-02-07 | New York University | Methods and agents for modulating protocadherin-18 activity |
| EP2906684B8 (en) * | 2012-10-10 | 2020-09-02 | Sangamo Therapeutics, Inc. | T cell modifying compounds and uses thereof |
| US9662402B2 (en) | 2012-10-16 | 2017-05-30 | Endocyte, Inc. | Drug delivery conjugates containing unnatural amino acids and methods for using |
| PT2992017T (pt) | 2013-05-02 | 2021-01-29 | Anaptysbio Inc | Anticorpos dirigidos contra a morte programada 1 (pd-1) |
| WO2014197369A1 (en) * | 2013-06-06 | 2014-12-11 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identification, assessment prevention, and treatment of cancer using pd-l1 isoforms |
| JP2016532711A (ja) | 2013-09-06 | 2016-10-20 | オーリジーン ディスカバリー テクノロジーズ リミテッドAurigene Discovery Technologies Limited | 免疫調節剤としての1,3,4−オキサジアゾール及び1,3,4−チアジアゾールの誘導体 |
| JP6521977B2 (ja) | 2013-09-06 | 2019-05-29 | オーリジーン ディスカバリー テクノロジーズ リミテッドAurigene Discovery Technologies Limited | 免疫調節剤としての1,2,4−オキサジアゾール誘導体 |
| KR20160075506A (ko) | 2013-09-06 | 2016-06-29 | 오리진 디스커버리 테크놀로지스 리미티드 | 면역조절제로서 사이클릭 펩티도미메틱 화합물 |
| US10570204B2 (en) | 2013-09-26 | 2020-02-25 | The Medical College Of Wisconsin, Inc. | Methods for treating hematologic cancers |
| RU2732604C2 (ru) | 2013-12-20 | 2020-09-21 | Интервет Интернэшнл Б.В. | Антитела к pd-1 собак |
| JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
| JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
| EP3660050A1 (en) | 2014-03-14 | 2020-06-03 | Novartis AG | Antibody molecules to lag-3 and uses thereof |
| CA2954446A1 (en) | 2014-07-09 | 2016-01-14 | Shanghai Birdie Biotech, Inc. | Anti-pd-l1 combinations for treating tumors |
| CN112546238A (zh) | 2014-09-01 | 2021-03-26 | 博笛生物科技有限公司 | 用于治疗肿瘤的抗-pd-l1结合物 |
| KR20170060042A (ko) | 2014-09-13 | 2017-05-31 | 노파르티스 아게 | Alk 억제제의 조합 요법 |
| SMT202200163T1 (it) | 2015-03-10 | 2022-05-12 | Aurigene Discovery Tech Ltd | Composti di 1,2,4-0ssadiazolo e tiadiazolo come immunomodulatori |
| WO2016149201A2 (en) | 2015-03-13 | 2016-09-22 | Cytomx Therapeutics, Inc. | Anti-pdl1 antibodies, activatable anti-pdl1 antibodies, and methods of use thereof |
| WO2016196218A1 (en) | 2015-05-31 | 2016-12-08 | Curegenix Corporation | Combination compositions for immunotherapy |
| BR112018000768A2 (pt) | 2015-07-13 | 2018-09-25 | Cytomx Therapeutics Inc | anticorpos anti-pd-1, anticorpos anti-pd-1 ativáveis e métodos de uso dos mesmos |
| WO2017009842A2 (en) | 2015-07-16 | 2017-01-19 | Biokine Therapeutics Ltd. | Compositions and methods for treating cancer |
| WO2017024465A1 (en) | 2015-08-10 | 2017-02-16 | Innovent Biologics (Suzhou) Co., Ltd. | Pd-1 antibodies |
| KR20180054824A (ko) | 2015-09-29 | 2018-05-24 | 셀진 코포레이션 | Pd-1 결합 단백질 및 이의 사용 방법 |
| CA3005696A1 (en) | 2015-12-18 | 2017-06-22 | Intervet International B.V. | Caninized human antibodies to human and canine il-4r alpha |
| US11091556B2 (en) | 2015-12-18 | 2021-08-17 | Intervet Inc. | Caninized human antibodies to human IL-4R alpha |
| KR20190080825A (ko) | 2016-03-21 | 2019-07-08 | 다나-파버 캔서 인스티튜트 인크. | T-세포 기능소실 상태-특이적 유전자 발현 조절인자 및 그 용도 |
| EP3472180A1 (en) | 2016-06-21 | 2019-04-24 | IO Biotech APS | Pdl1 peptides for use in cancer vaccines |
| US11317611B2 (en) | 2016-08-31 | 2022-05-03 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animal with human or chimeric PD-L1 |
| CN107815466B (zh) | 2016-08-31 | 2020-03-13 | 百奥赛图江苏基因生物技术有限公司 | 人源化基因改造动物模型的制备方法及应用 |
| ES2837755T3 (es) | 2016-09-14 | 2021-07-01 | Abbvie Biotherapeutics Inc | Anticuerpos anti-PD-1 |
| BR112019004733A2 (pt) | 2016-09-19 | 2019-05-28 | Celgene Corp | métodos de tratamento de distúrbios imunes usando proteínas de ligação a pd-1 |
| US10766958B2 (en) | 2016-09-19 | 2020-09-08 | Celgene Corporation | Methods of treating vitiligo using PD-1 binding antibodies |
| WO2018071809A1 (en) * | 2016-10-14 | 2018-04-19 | Ariad Pharmaceuticals, Inc. | Inducible t-cell system and uses thereof |
| US11155624B2 (en) | 2016-11-01 | 2021-10-26 | Anaptysbio, Inc. | Antibodies directed against programmed death-1 (PD-1) |
| CN110382545A (zh) | 2017-01-09 | 2019-10-25 | 泰萨罗公司 | 用抗pd-1抗体治疗癌症的方法 |
| CN110914302A (zh) | 2017-06-01 | 2020-03-24 | 赛托姆克斯治疗学股份有限公司 | 可活化抗pdl1抗体及其使用方法 |
| CA3061959A1 (en) | 2017-06-09 | 2018-12-13 | Providence Health & Services - Oregon | Utilization of cd39 and cd103 for identification of human tumor reactive t cells for treatment of cancer |
| CN111133315A (zh) | 2017-08-11 | 2020-05-08 | 得克萨斯州大学系统董事会 | 用于治疗癌症转移的靶向激酶 |
| WO2019061324A1 (en) | 2017-09-29 | 2019-04-04 | Curis Inc. | CRYSTALLINE FORMS OF IMMUNOMODULATORS |
| US11136300B2 (en) | 2017-10-11 | 2021-10-05 | Aurigene Discovery Technologies Limited | Crystalline forms of 3-substituted 1,2,4-oxadiazole |
| JP7378394B2 (ja) | 2017-11-03 | 2023-11-13 | オーリジーン オンコロジー リミテッド | Tim-3およびpd-1経路の二重阻害剤 |
| WO2019087092A1 (en) | 2017-11-06 | 2019-05-09 | Aurigene Discovery Technologies Limited | Conjoint therapies for immunomodulation |
| JP2021502405A (ja) * | 2017-11-08 | 2021-01-28 | エピアクシス セラピューティクス プロプライエタリー リミテッド | 免疫原性組成物及びその使用 |
| CN112292185B (zh) | 2018-04-17 | 2025-07-29 | 塞德斯医疗公司 | 抗cd27和抗pd-l1抗体及双特异性构建体 |
| CN108828227B (zh) * | 2018-05-17 | 2020-06-30 | 浙江大学 | PD-L1剪接体c作为预测肿瘤预后靶标的应用 |
| MA56533A (fr) | 2019-06-18 | 2022-04-27 | Janssen Sciences Ireland Unlimited Co | Combinaison de vaccins contre le virus de l'hépatite b (vhb) et d'anticorps anti-pd-1 |
| JP2022536850A (ja) | 2019-06-18 | 2022-08-19 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | B型肝炎ウイルス(hbv)ワクチンおよび抗pd-1または抗pd-l1抗体の組合せ |
| CN113030475B (zh) * | 2021-05-25 | 2021-08-10 | 泛肽生物科技(浙江)有限公司 | 一种基于细胞线粒体质量评估的t细胞pd-1检测方法 |
| AU2022288058A1 (en) | 2021-06-07 | 2023-11-16 | Agonox, Inc. | Cxcr5, pd-1, and icos expressing tumor reactive cd4 t cells and their use |
| NL2035804B1 (en) * | 2023-09-15 | 2025-03-25 | Umc Utrecht Holding Bv | Immune modulating inhibitory receptors |
Family Cites Families (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| EP0044167A3 (en) | 1980-07-14 | 1982-04-21 | The Regents Of The University Of California | Antibody targeted cytotoxic agent |
| NO812612L (no) | 1980-08-06 | 1982-02-08 | Ferring Pharma Ltd | Enzym-inhibitorer. |
| US4873191A (en) | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
| US4474893A (en) | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4870009A (en) | 1982-11-22 | 1989-09-26 | The Salk Institute For Biological Studies | Method of obtaining gene product through the generation of transgenic animals |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4736866A (en) | 1984-06-22 | 1988-04-12 | President And Fellows Of Harvard College | Transgenic non-human mammals |
| JPS6147500A (ja) | 1984-08-15 | 1986-03-07 | Res Dev Corp Of Japan | キメラモノクロ−ナル抗体及びその製造法 |
| EP0173494A3 (en) | 1984-08-27 | 1987-11-25 | The Board Of Trustees Of The Leland Stanford Junior University | Chimeric receptors by dna splicing and expression |
| GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
| JPS61134325A (ja) | 1984-12-04 | 1986-06-21 | Teijin Ltd | ハイブリツド抗体遺伝子の発現方法 |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| DE122007000007I2 (de) | 1986-04-09 | 2010-12-30 | Genzyme Corp | Genetisch transformierte Tiere, die ein gewünschtes Protein in Milch absondern |
| US4902505A (en) | 1986-07-30 | 1990-02-20 | Alkermes | Chimeric peptides for neuropeptide delivery through the blood-brain barrier |
| US4987071A (en) | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
| US5116742A (en) | 1986-12-03 | 1992-05-26 | University Patents, Inc. | RNA ribozyme restriction endoribonucleases and methods |
| US4904582A (en) | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
| US4873316A (en) | 1987-06-23 | 1989-10-10 | Biogen, Inc. | Isolation of exogenous recombinant proteins from the milk of transgenic mammals |
| US5080891A (en) | 1987-08-03 | 1992-01-14 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
| DE768377T1 (de) | 1988-09-02 | 1998-01-02 | Dyax Corp | Herstellung und Auswahl von Rekombinantproteinen mit verschiedenen Bindestellen |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5272057A (en) | 1988-10-14 | 1993-12-21 | Georgetown University | Method of detecting a predisposition to cancer by the use of restriction fragment length polymorphism of the gene for human poly (ADP-ribose) polymerase |
| US5116964A (en) | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
| FR2646438B1 (fr) | 1989-03-20 | 2007-11-02 | Pasteur Institut | Procede de remplacement specifique d'une copie d'un gene present dans le genome receveur par l'integration d'un gene different de celui ou se fait l'integration |
| US5328470A (en) | 1989-03-31 | 1994-07-12 | The Regents Of The University Of Michigan | Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor |
| US5459039A (en) | 1989-05-12 | 1995-10-17 | Duke University | Methods for mapping genetic mutations |
| DE69033493D1 (de) | 1989-07-25 | 2004-08-12 | Cell Genesys Inc | Homologe rekombination für universelle donorzellen und chimerische säugetierzellen |
| US5580756A (en) | 1990-03-26 | 1996-12-03 | Bristol-Myers Squibb Co. | B7Ig fusion protein |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| DK0585287T3 (da) | 1990-07-10 | 2000-04-17 | Cambridge Antibody Tech | Fremgangsmåde til fremstilling af specifikke bindingsparelementer |
| JPH06501679A (ja) | 1990-07-10 | 1994-02-24 | スミスクライン・ビーチャム・コーポレイション | オキサミド |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| EP0557300B1 (en) | 1990-10-29 | 1997-11-19 | Chiron Corporation | Bispecific antibodies, method of production, and uses thereof |
| CA2095633C (en) | 1990-12-03 | 2003-02-04 | Lisa J. Garrard | Enrichment method for variant proteins with altered binding properties |
| ES2287206T3 (es) | 1991-03-01 | 2007-12-16 | Dyax Corporation | Proceso para el desarrollo de mini-proteinas de union. |
| WO1992018619A1 (en) | 1991-04-10 | 1992-10-29 | The Scripps Research Institute | Heterodimeric receptor libraries using phagemids |
| US5871907A (en) | 1991-05-15 | 1999-02-16 | Medical Research Council | Methods for producing members of specific binding pairs |
| US5844095A (en) | 1991-06-27 | 1998-12-01 | Bristol-Myers Squibb Company | CTLA4 Ig fusion proteins |
| DE4122599C2 (de) | 1991-07-08 | 1993-11-11 | Deutsches Krebsforsch | Phagemid zum Screenen von Antikörpern |
| AU2515992A (en) | 1991-08-20 | 1993-03-16 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| US5660827A (en) | 1992-03-05 | 1997-08-26 | Board Of Regents, The University Of Texas System | Antibodies that bind to endoglin |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| AU685054C (en) | 1992-05-14 | 2003-02-27 | Baylor College Of Medicine | Mutated steroid hormone receptors, methods for their use and molecular switch for gene therapy |
| WO1994002610A1 (en) | 1992-07-17 | 1994-02-03 | Dana-Farber Cancer Institute | Method of intracellular binding of target molecules |
| MX9304769A (es) | 1992-08-05 | 1994-05-31 | Max Planck Gesellschaft | Subfamilia ptp-d de fosfatasas de la proteina tirosina. |
| US5589375A (en) | 1992-10-06 | 1996-12-31 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E. V. | PTP 1D: a novel protein tyrosine phosphatase |
| EP1362913B1 (en) | 1992-10-30 | 2006-01-25 | The General Hospital Corporation | Interaction trap system for isolating proteins |
| EP0679196B1 (en) | 1993-01-07 | 2004-05-26 | Sequenom, Inc. | Dna sequencing by mass spectrometry |
| JP3824633B2 (ja) | 1993-02-12 | 2006-09-20 | ザ・ボード・オブ・トラスティーズ・オブ・ザ・リランド・スタンフォード・ジュニアー・ユニバーシティ | 標的遺伝子の調節的転写および他の生物学的結果 |
| AU7052194A (en) | 1993-06-04 | 1995-01-03 | Regents Of The University Of Michigan, The | Methods for selectively stimulating proliferation of t cells |
| US5866755A (en) | 1993-06-14 | 1999-02-02 | Basf Aktiengellschaft | Animals transgenic for a tetracycline-regulated transcriptional inhibitor |
| WO1994029442A2 (en) | 1993-06-14 | 1994-12-22 | Basf Aktiengesellschaft | Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters |
| CA2168349A1 (en) | 1993-07-30 | 1995-02-09 | Lingxun Duan | Intracellular immunization |
| UA40577C2 (uk) | 1993-08-02 | 2001-08-15 | Мерк Патент Гмбх | Біспецифічна молекула, що використовується для лізису пухлинних клітин, спосіб її одержання, моноклональне антитіло (варіанти), фармацевтичний препарат, фармацевтичний набір (варіанти), спосіб видалення пухлинних клітин |
| US5498531A (en) | 1993-09-10 | 1996-03-12 | President And Fellows Of Harvard College | Intron-mediated recombinant techniques and reagents |
| JPH07291996A (ja) | 1994-03-01 | 1995-11-07 | Yuu Honshiyo | ヒトにおけるプログラムされた細胞死に関連したポリペプチド、それをコードするdna、そのdnaからなるベクター、そのベクターで形質転換された宿主細胞、そのポリペプチドの抗体、およびそのポリペプチドまたはその抗体を含有する薬学的組成物 |
| US6576236B1 (en) * | 1994-07-01 | 2003-06-10 | Dana Farber Cancer Institute | Methods for stimulating T cell responses by manipulating a common cytokine receptor γ chain |
| GB9517780D0 (en) | 1995-08-31 | 1995-11-01 | Roslin Inst Edinburgh | Biological manipulation |
| GB9517779D0 (en) | 1995-08-31 | 1995-11-01 | Roslin Inst Edinburgh | Biological manipulation |
| US6750334B1 (en) | 1996-02-02 | 2004-06-15 | Repligen Corporation | CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor |
| AU3307497A (en) | 1996-06-26 | 1998-01-14 | Antigen Express, Inc. | Immunotherapy by modulation of antigen presentation |
| US6040152A (en) * | 1996-12-31 | 2000-03-21 | National Jewish Medical And Research Center | Method and assay for regulation of T cell proliferation |
| JP3521382B2 (ja) | 1997-02-27 | 2004-04-19 | 日本たばこ産業株式会社 | 細胞間接着及びシグナル伝達を媒介する細胞表面分子 |
| DK1210428T3 (en) | 1999-08-23 | 2015-06-15 | Dana Farber Cancer Inst Inc | PD-1, a receptor for B7-4 AND USE THEREOF |
| IL148021A0 (en) | 1999-08-23 | 2002-09-12 | Dana Farber Cancer Inst Inc | Novel b7-4 molecules and uses therefor |
| EP2388590A1 (en) * | 2001-04-02 | 2011-11-23 | Dana Farber Cancer Institute | PD-1, a receptor for B7-4, and uses thereof |
| IT1395574B1 (it) | 2009-09-14 | 2012-10-16 | Guala Dispensing Spa | Dispositivo di erogazione |
-
2002
- 2002-04-02 EP EP10191193A patent/EP2388590A1/en not_active Withdrawn
- 2002-04-02 BR BR0208637-9A patent/BR0208637A/pt not_active IP Right Cessation
- 2002-04-02 WO PCT/US2002/010371 patent/WO2002079499A1/en not_active Ceased
- 2002-04-02 EP EP02757942A patent/EP1383912A4/en not_active Withdrawn
- 2002-04-02 MX MXPA03008959A patent/MXPA03008959A/es active IP Right Grant
- 2002-04-02 NZ NZ528265A patent/NZ528265A/en unknown
- 2002-04-02 CA CA002442066A patent/CA2442066C/en not_active Expired - Lifetime
- 2002-04-02 AU AU2002338272A patent/AU2002338272B2/en not_active Ceased
- 2002-04-02 US US10/115,615 patent/US7105328B2/en not_active Expired - Lifetime
- 2002-04-02 JP JP2002577908A patent/JP2004533226A/ja active Pending
- 2002-04-02 PL PL02367162A patent/PL367162A1/xx unknown
-
2003
- 2003-09-18 ZA ZA200307310A patent/ZA200307310B/en unknown
- 2003-10-01 NO NO20034387A patent/NO20034387L/no not_active Application Discontinuation
-
2006
- 2006-09-11 US US11/519,186 patent/US7700301B2/en not_active Expired - Fee Related
-
2010
- 2010-04-16 US US12/761,704 patent/US20110033884A1/en not_active Abandoned
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| US7105328B2 (en) | 2006-09-12 |
| US20080274490A1 (en) | 2008-11-06 |
| CA2442066A1 (en) | 2002-10-10 |
| US20030044768A1 (en) | 2003-03-06 |
| PL367162A1 (en) | 2005-02-21 |
| EP2388590A1 (en) | 2011-11-23 |
| BR0208637A (pt) | 2004-12-07 |
| NO20034387L (no) | 2003-11-28 |
| US20110033884A1 (en) | 2011-02-10 |
| US7700301B2 (en) | 2010-04-20 |
| EP2388590A8 (en) | 2011-12-28 |
| AU2002338272B2 (en) | 2007-10-11 |
| CA2442066C (en) | 2005-11-01 |
| MXPA03008959A (es) | 2004-10-15 |
| ZA200307310B (en) | 2004-09-20 |
| WO2002079499A1 (en) | 2002-10-10 |
| JP2004533226A (ja) | 2004-11-04 |
| EP1383912A4 (en) | 2007-11-28 |
| NO20034387D0 (no) | 2003-10-01 |
| EP1383912A1 (en) | 2004-01-28 |
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