TWI605061B - 會結合及阻斷表現在骨髓細胞上觸發受體－１（ｔｒｅｍ－１）之抗體 - Google Patents
會結合及阻斷表現在骨髓細胞上觸發受體－１（ｔｒｅｍ－１）之抗體 Download PDFInfo
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07K16/2803—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
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- C—CHEMISTRY; METALLURGY
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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| TWI716405B (zh) | 2015-05-07 | 2021-01-21 | 美商艾吉納斯公司 | 抗ox40抗體及其使用方法 |
| WO2017083682A1 (en) * | 2015-11-12 | 2017-05-18 | The Board Of Trustees Of Leland Stanford Junior University | Labeled probe and methods of use |
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| CN108276488B (zh) * | 2018-01-26 | 2020-06-19 | 四川农业大学 | 一种鸡髓样细胞触发受体b2多克隆抗体及其制备方法和应用 |
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| EP3836951A1 (en) | 2018-08-13 | 2021-06-23 | Signablok, Inc. | Peptides and compositions for targeted treatment and imaging |
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| US10836828B2 (en) | 2019-02-06 | 2020-11-17 | Pionyr Immunotherapeutics, Inc. | Anti-TREM1 antibodies and related methods |
| JP2022540904A (ja) * | 2019-07-15 | 2022-09-20 | ブリストル－マイヤーズ スクイブ カンパニー | ヒトｔｒｅｍ－１に対する抗体およびその使用 |
| CN114174536A (zh) * | 2019-07-15 | 2022-03-11 | 百时美施贵宝公司 | 抗trem-1抗体及其用途 |
| EP4065152A1 (en) | 2019-11-25 | 2022-10-05 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Trem-1 inhibitors for the treatment of vaso-occlusions and tissue injuries in patients suffering from sickle cell disease |
| CN111157741B (zh) * | 2019-12-30 | 2022-08-16 | 广州市妇女儿童医疗中心 | 髓系细胞触发受体1在制备胃炎诊断或治疗试剂中的应用及试剂盒 |
| EP4161551A1 (en) | 2020-06-05 | 2023-04-12 | Inotrem | Trem-1 inhibitor for use in the treatment of a subject suffering from a coronavirus infection |
| CA3181469A1 (en) | 2020-06-05 | 2021-12-09 | Jean-Jacques GARAUD | Soluble trem-1 as a marker of severity or complications for a subject suffering from a coronavirus infection |
| CN116782929A (zh) | 2020-11-02 | 2023-09-19 | Ucb生物制药有限责任公司 | 抗-trem1中和抗体用于治疗运动神经元变性病症的用途 |
| WO2022189659A1 (en) | 2021-03-12 | 2022-09-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Trem-1 inhibitors for the treatment of marfan syndrome |
| CN117642428A (zh) * | 2021-05-03 | 2024-03-01 | Ucb生物制药有限责任公司 | 抗体 |
| US20240254225A1 (en) * | 2021-06-02 | 2024-08-01 | Inotrem | Anti-trem-1 antibodies |
| EP4416501A1 (en) | 2021-10-11 | 2024-08-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of trem-1 for predicting and preventing postoperative complications after cardiac surgery with cardiopulmonary by-pass |
| CN114948849A (zh) * | 2022-05-13 | 2022-08-30 | 苏州大学附属第一医院 | 一种含trem1抑制剂的微针、微针系统及其制备方法 |
| CN115586338A (zh) * | 2022-09-20 | 2023-01-10 | 杭州赛基生物科技有限公司 | 用于检测可溶性细胞因子受体的试剂盒及其制备方法 |
| AU2024257984A1 (en) | 2023-04-21 | 2025-10-02 | Celsius Therapeutics, Inc. | Anti-trem1 antibody agents, compositions, and uses thereof |
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Family Cites Families (171)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| US4873191A (en) | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
| 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 |
| US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
| US4741900A (en) | 1982-11-16 | 1988-05-03 | Cytogen Corporation | Antibody-metal ion complexes |
| 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 |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| 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 |
| US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
| US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| DE122007000007I1 (de) | 1986-04-09 | 2007-05-16 | 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 |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| JP2972257B2 (ja) | 1990-01-24 | 1999-11-08 | 株式会社日立製作所 | パケット交換機 |
| US5116742A (en) | 1986-12-03 | 1992-05-26 | University Patents, Inc. | RNA ribozyme restriction endoribonucleases and methods |
| US4987071A (en) | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
| US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
| 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 |
| US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| DE68927933T2 (de) | 1988-09-02 | 1997-08-14 | Dyax Corp | Herstellung und auswahl von rekombinantproteinen mit verschiedenen bindestellen |
| 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 |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized 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 |
| DE69034263D1 (de) | 1989-07-25 | 2009-04-02 | Cell Genesys Inc | Homologe Rekombination für universelle Donorzellen und chimerische Säugetierzellen |
| US5413923A (en) | 1989-07-25 | 1995-05-09 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
| US5436146A (en) | 1989-09-07 | 1995-07-25 | The Trustees Of Princeton University | Helper-free stocks of recombinant adeno-associated virus vectors |
| WO1991006667A1 (en) | 1989-11-06 | 1991-05-16 | Cell Genesys, Inc. | Production of proteins using homologous recombination |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| US5272071A (en) | 1989-12-22 | 1993-12-21 | Applied Research Systems Ars Holding N.V. | Method for the modification of the expression characteristics of an endogenous gene of a given cell line |
| WO1991010737A1 (en) | 1990-01-11 | 1991-07-25 | Molecular Affinities Corporation | Production of antibodies using gene libraries |
| US5780225A (en) | 1990-01-12 | 1998-07-14 | Stratagene | Method for generating libaries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules |
| DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| MA22668A1 (fr) | 1990-07-10 | 1993-07-01 | Smithkline Beecham Corp | Procede de preparation d'oxamides . |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| WO1992003918A1 (en) | 1990-08-29 | 1992-03-19 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5698426A (en) | 1990-09-28 | 1997-12-16 | Ixsys, Incorporated | Surface expression libraries of heteromeric receptors |
| WO1992006180A1 (en) | 1990-10-01 | 1992-04-16 | University Of Connecticut | Targeting viruses and cells for selective internalization by cells |
| DK0564531T3 (da) | 1990-12-03 | 1998-09-28 | Genentech Inc | Berigelsesfremgangsmåde for variantproteiner med ændrede bindingsegenskaber |
| DK1471142T3 (da) | 1991-04-10 | 2009-03-09 | Scripps Research Inst | Heterodimere receptor-biblioteker under anvendelse af fagemider |
| EP0584279B1 (en) | 1991-05-14 | 2001-03-14 | The University Of Connecticut | Targeted delivery of genes encoding immunogenic proteins |
| DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
| WO1992022635A1 (en) | 1991-06-05 | 1992-12-23 | University Of Connecticut | Targeted delivery of genes encoding secretory proteins |
| CA2110799A1 (en) | 1991-06-14 | 1992-12-23 | Arnold H. Horwitz | Microbially-produced antibody fragments and their conjugates |
| WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | 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 |
| DE69233745D1 (de) | 1991-12-02 | 2008-10-23 | Cambridge Antibody Tech | Herstellung von Autoantikörpern auf Phagenoberflächen ausgehend von Antikörpersegmentbibliotheken |
| AU3434393A (en) | 1992-01-17 | 1993-08-03 | Regents Of The University Of Michigan, The | Targeted virus |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| CA2133411A1 (en) | 1992-04-03 | 1993-10-14 | Alexander T. YOUNG | Gene therapy using targeted viral vectors |
| ZA932522B (en) | 1992-04-10 | 1993-12-20 | Res Dev Foundation | Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens |
| FR2694851B1 (fr) | 1992-08-12 | 1994-12-23 | Sgs Thomson Microelectronics | Circuit de tirage vers un état déterminé d'une entrée de circuit intégré. |
| JPH08501085A (ja) | 1992-08-26 | 1996-02-06 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 抗腫瘍剤としてのサイトカインｉｐ−１０の利用 |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| ATE200625T1 (de) | 1992-10-09 | 2001-05-15 | Advanced Tissue Sciences Inc | Leberreservezellen |
| CA2148252C (en) | 1992-10-30 | 2007-06-12 | Roger Brent | Interaction trap system for isolating novel proteins |
| JPH08503855A (ja) | 1992-12-03 | 1996-04-30 | ジェンザイム・コーポレイション | 嚢胞性線維症に対する遺伝子治療 |
| EP1262564A3 (en) | 1993-01-07 | 2004-03-31 | Sequenom, Inc. | Dna sequencing by mass spectrometry |
| US5424286A (en) | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
| US5498531A (en) | 1993-09-10 | 1996-03-12 | President And Fellows Of Harvard College | Intron-mediated recombinant techniques and reagents |
| JPH09506262A (ja) | 1993-12-08 | 1997-06-24 | ジェンザイム・コーポレイション | 特異的抗体の製造方法 |
| DE69534347T2 (de) | 1994-01-31 | 2006-05-24 | Trustees Of Boston University, Boston | Bibliotheken aus Polyklonalen Antikörpern |
| US5516637A (en) | 1994-06-10 | 1996-05-14 | Dade International Inc. | Method involving display of protein binding pairs on the surface of bacterial pili and bacteriophage |
| ATE390933T1 (de) | 1995-04-27 | 2008-04-15 | Amgen Fremont Inc | Aus immunisierten xenomäusen stammende menschliche antikörper gegen il-8 |
| WO1996034096A1 (en) | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| GB9517779D0 (en) | 1995-08-31 | 1995-11-01 | Roslin Inst Edinburgh | Biological manipulation |
| GB9517780D0 (en) | 1995-08-31 | 1995-11-01 | Roslin Inst Edinburgh | Biological manipulation |
| JP2978435B2 (ja) | 1996-01-24 | 1999-11-15 | チッソ株式会社 | アクリロキシプロピルシランの製造方法 |
| IL128332A0 (en) | 1996-08-30 | 2000-01-31 | Novo Nordisk As | GLP-1 derivatives |
| US6034217A (en) | 1996-09-17 | 2000-03-07 | Wako Pure Chemical Industries, Ltd. | Peptidoglycan recognition proteins and their production |
| US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
| CA2722378C (en) | 1996-12-03 | 2015-02-03 | Amgen Fremont Inc. | Human antibodies that bind tnf.alpha. |
| CA2283299A1 (en) | 1997-03-07 | 1998-09-11 | Human Genome Sciences, Inc. | 186 human secreted proteins |
| WO1998039446A2 (en) | 1997-03-07 | 1998-09-11 | Human Genome Sciences, Inc. | 70 human secreted proteins |
| US20030175858A1 (en) | 1997-03-07 | 2003-09-18 | Ruben Steven M. | 186 human secreted proteins |
| US20030049618A1 (en) | 1997-03-07 | 2003-03-13 | Ruben Steven M. | 186 human secreted proteins |
| US6420526B1 (en) | 1997-03-07 | 2002-07-16 | Human Genome Sciences, Inc. | 186 human secreted proteins |
| US6878687B1 (en) | 1997-03-07 | 2005-04-12 | Human Genome Sciences, Inc. | Protein HMAAD57 |
| US7227002B1 (en) | 1997-04-14 | 2007-06-05 | Micromet Ag | Human antibodies that bind human 17-A1/EpCAM tumor antigen |
| WO1998048837A1 (en) | 1997-04-30 | 1998-11-05 | Enzon, Inc. | Polyalkylene oxide-modified single chain polypeptides |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| US6172211B1 (en) | 1997-07-11 | 2001-01-09 | Boehringer Ingelheim International Gmbh | Nucleic acid encoding tag7 polypeptide |
| EP1022286A4 (en) | 1997-10-07 | 2003-04-09 | Ono Pharmaceutical Co | POLYPEPTIDES, FOR ENDING CODNA AND THEIR USE |
| WO2000000610A2 (en) | 1998-06-26 | 2000-01-06 | Incyte Pharmaceuticals, Inc. | Human signal peptide-containing proteins |
| US6858204B2 (en) | 1999-06-30 | 2005-02-22 | Corxia Corporation | Compositions and methods for the therapy and diagnosis of lung cancer |
| US6509448B2 (en) | 1999-06-30 | 2003-01-21 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of lung cancer |
| US20030211510A1 (en) | 1999-06-30 | 2003-11-13 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of lung cancer |
| US20020197669A1 (en) | 2000-12-13 | 2002-12-26 | Bangur Chaitanya S. | Compositions and methods for the therapy and diagnosis of lung cancer |
| US20030170255A1 (en) | 1999-06-30 | 2003-09-11 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of lung cancer |
| US6504010B1 (en) | 1999-06-30 | 2003-01-07 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of lung cancer |
| US20020172952A1 (en) | 1999-06-30 | 2002-11-21 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of lung cancer |
| CA2402563A1 (en) | 1999-12-23 | 2001-07-26 | Hyseq, Inc. | Novel nucleic acids and polypeptides |
| AU2001274888A1 (en) | 2000-05-19 | 2001-12-03 | Human Genome Sciences, Inc. | Nucleic acids, proteins, and antibodies |
| US20030134283A1 (en) | 2000-10-03 | 2003-07-17 | Peterson David P. | Genes regulated in dendritic cell differentiation |
| WO2002058721A1 (en) | 2000-12-08 | 2002-08-01 | Baylor College Of Medicine | Trem-1 splice variant for use in modifying immune responses |
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| CA2342376C (en) | 2001-03-20 | 2013-11-12 | Marco Colonna | A receptor trem (triggering receptor expressed on myeloid cells) and uses thereof |
| US8231878B2 (en) | 2001-03-20 | 2012-07-31 | Cosmo Research & Development S.P.A. | Receptor trem (triggering receptor expressed on myeloid cells) and uses thereof |
| WO2003029401A2 (en) | 2001-07-13 | 2003-04-10 | Advanced Research And Technology Institute | Peptidoglycan recognition protein encoding nucleic acids and methods of use thereof |
| WO2003011213A2 (en) | 2001-07-30 | 2003-02-13 | Eli Lilly And Company | Method for treating diabetes and obesity |
| JP2005518782A (ja) | 2001-09-17 | 2005-06-30 | プロテイン デザイン ラブス， インコーポレイテッド | ガンの診断方法、ガンのモジュレータのスクリーニング組成物及び方法 |
| EP2072059A1 (en) | 2001-10-12 | 2009-06-24 | Schering Corporation | Use of bispecific antibodies to regulate immune responses |
| AU2002364586A1 (en) | 2001-12-21 | 2003-07-30 | Delta Biotechnology Limited | Albumin fusion proteins |
| EP1329227A1 (en) | 2002-01-22 | 2003-07-23 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Diagnostic conjugate useful for intercellular imaging and for differentiating between tumor- and non-tumor cells |
| AU2003215761A1 (en) | 2002-03-22 | 2003-10-08 | Bioxell S.P.A. | A novel receptor trem (triggering receptor expressed on myeloid cells) and uses thereof |
| WO2004020591A2 (en) | 2002-08-29 | 2004-03-11 | Five Prime Therapeutics, Inc. | Methods of use for novel human polypeptides encoded by polynucleotides |
| GB0305478D0 (en) | 2003-03-10 | 2003-04-16 | Bioxell Spa | Diagnostic and prognostic compounds and method |
| US20050255114A1 (en) | 2003-04-07 | 2005-11-17 | Nuvelo, Inc. | Methods and diagnosis for the treatment of preeclampsia |
| DE10316701A1 (de) | 2003-04-09 | 2004-11-04 | Hinzmann, Bernd, Dr. | Humane Nukleinsäuresequenzen aus Bronchialkarzinomen |
| WO2005005601A2 (en) | 2003-06-09 | 2005-01-20 | The Regents Of The University Of Michigan | Compositions and methods for treating and diagnosing cancer |
| WO2005040219A1 (en) | 2003-10-28 | 2005-05-06 | Novo Nordisk A/S | Laminin-5 gamma2-binding peptides, related compositions, and use thereof |
| EP1692506A4 (en) | 2003-11-17 | 2008-01-09 | Janssen Pharmaceutica Nv | MODELING A SYSTEMIC INFLAMMATORY RESPONSE TO INFECTION |
| GB0401730D0 (en) | 2004-01-27 | 2004-03-03 | Bioxell Spa | Diagnosis method |
| CA2557782A1 (en) | 2004-03-17 | 2005-10-06 | Eli Lilly And Company | Glycol linked fgf-21 compounds |
| DE602005016917D1 (de) | 2004-05-13 | 2009-11-12 | Lilly Co Eli | Fgf-21-fusionsproteine |
| WO2006028714A1 (en) | 2004-09-02 | 2006-03-16 | Eli Lilly And Company | Muteins of fibroblast growth factor 21 |
| EA011390B1 (ru) | 2004-09-02 | 2009-02-27 | Эли Лилли Энд Компани | Мутантные белки (мутеины) фактора роста фибробластов 21 |
| GB0426146D0 (en) | 2004-11-29 | 2004-12-29 | Bioxell Spa | Therapeutic peptides and method |
| JP2008522617A (ja) | 2004-12-14 | 2008-07-03 | イーライ リリー アンド カンパニー | 線維芽細胞成長因子２１の突然変異タンパク質 |
| WO2006078463A2 (en) | 2005-01-21 | 2006-07-27 | Eli Lilly And Company | Method for treating cardiovascular disease |
| TWI362392B (en) | 2005-03-18 | 2012-04-21 | Novo Nordisk As | Acylated glp-1 compounds |
| WO2006138275A2 (en) | 2005-06-13 | 2006-12-28 | The Regents Of The University Of Michigan | Compositions and methods for treating and diagnosing cancer |
| WO2006135886A2 (en) | 2005-06-13 | 2006-12-21 | The Regents Of The University Of Michigan | Compositions and methods for treating and diagnosing cancer |
| CN105837690A (zh) | 2006-06-12 | 2016-08-10 | 新兴产品开发西雅图有限公司 | 具有效应功能的单链多价结合蛋白 |
| EP2465510B1 (en) | 2006-10-19 | 2018-11-28 | Baylor College Of Medicine | Methods and compositions for generating an immune response by inducing CD40 and pattern recognition receptors and adaptors thereof |
| AU2008205538A1 (en) * | 2007-01-16 | 2008-07-24 | Wyeth | Inflammation treatment, detection and monitoring via TREM-1 |
| CN107501407B (zh) | 2007-03-30 | 2022-03-18 | Ambrx公司 | 经修饰fgf-21多肽和其用途 |
| CA2694488A1 (en) | 2007-07-31 | 2009-02-05 | Medimmune, Llc | Multispecific epitope binding proteins and uses thereof |
| US20110034373A1 (en) | 2007-08-03 | 2011-02-10 | Eli Lilly And Company | Use of an fgf-21 compound and a glp-1 compound for the treatment of obesity |
| US8933197B2 (en) | 2007-08-15 | 2015-01-13 | Amunix Operating Inc. | Compositions comprising modified biologically active polypeptides |
| WO2009030771A1 (en) | 2007-09-05 | 2009-03-12 | Novo Nordisk A/S | Peptides derivatized with a-b-c-d- and their therapeutical use |
| JP2011508219A (ja) | 2007-12-19 | 2011-03-10 | シンギュレックス・インコーポレイテッド | 単一分子検出走査分析器およびその使用方法 |
| US20090234202A1 (en) | 2008-03-05 | 2009-09-17 | Goix Philippe J | Method and compositions for highly sensitive detection of molecules |
| EP2796878A1 (en) | 2008-05-23 | 2014-10-29 | Biocartis NV | New biomarkers for diagnosis, prediction and/or prognosis of sepsis and uses thereof |
| MX2010014574A (es) | 2008-07-08 | 2011-04-27 | Abbott Lab | Inmunoglobulinas de dominio variable dual para prostaglandina e2 y usos de las mismas. |
| ES2445892T3 (es) | 2008-08-25 | 2014-03-05 | Janssen Biotech, Inc. | Biomarcadores para el tratamiento anti-TNF en colitis ulcerosa y trastornos relacionados |
| SG195542A1 (en) | 2008-10-10 | 2013-12-30 | Amgen Inc | Fgf21 mutants and uses thereof |
| WO2010065439A1 (en) | 2008-12-05 | 2010-06-10 | Eli Lilly And Company | Variants of fibroblast growth factor 21 |
| ES2692495T3 (es) | 2009-01-23 | 2018-12-03 | Novo Nordisk A/S | Derivados del FGF21 con aglutinante de albúmina A-B-C-D-E- y sus usos |
| WO2010132370A2 (en) | 2009-05-11 | 2010-11-18 | Government Of The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Soluble tlt-1 for the treatment and diagnosis of sepsis |
| US8911960B2 (en) | 2009-06-01 | 2014-12-16 | Case Western Reserve University | Method for identifying idiopathic pneumonia progression by measuring the level of mannose-binding protein C |
| EP2440235A1 (en) | 2009-06-11 | 2012-04-18 | Novo Nordisk A/S | Glp-1 and fgf21 combinations for treatment of diabetes type 2 |
| WO2011005481A1 (en) | 2009-06-22 | 2011-01-13 | Medimmune, Llc | ENGINEERED Fc REGIONS FOR SITE-SPECIFIC CONJUGATION |
| WO2011028952A1 (en) | 2009-09-02 | 2011-03-10 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| WO2011047097A2 (en) | 2009-10-13 | 2011-04-21 | Sigalov Alexander B | Inhibition of trem receptor signaling with peptide variants |
| KR101251023B1 (ko) | 2009-11-05 | 2013-04-03 | 주식회사유한양행 | 신규한 단일클론항체를 포함하는 박테리아 감염 검출용 키트 |
| EP2507381A4 (en) | 2009-12-04 | 2016-07-20 | Hoffmann La Roche | MULTISPECIFIC ANTIBODIES, ANTIBODY ANALOGS, COMPOSITIONS AND METHODS |
| US8362210B2 (en) | 2010-01-19 | 2013-01-29 | Xencor, Inc. | Antibody variants with enhanced complement activity |
| EA201291133A1 (ru) | 2010-04-30 | 2013-04-30 | Алексион Фармасьютикалз, Инк. | Антитела, обладающие пониженной иммуногенностью в организме человека |
| JP6014596B2 (ja) | 2010-11-09 | 2016-10-25 | メディミューン，エルエルシー | 均一コンジュゲーションのための抗体足場 |
| EP2655415A4 (en) | 2010-12-22 | 2016-03-09 | Abbvie Inc | THREE VARIABLE DOMAIN LINK PROTEINS AND USES THEREOF |
| WO2012088302A2 (en) | 2010-12-22 | 2012-06-28 | Abbott Laboratories | Half immunoglobulin binding proteins and uses thereof |
| US20140088019A1 (en) | 2011-02-11 | 2014-03-27 | Zyngenia, Inc. | Monovalent and Multivalent Multispecific Complexes and Uses Thereof |
| US9856365B2 (en) * | 2011-08-31 | 2018-01-02 | Radici Plastics Usa, Inc. | Compositions of polyhydric alcohols and polyamides |
| WO2013120553A1 (en) * | 2012-02-15 | 2013-08-22 | Novo Nordisk A/S | Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (trem-1) |
-
2012
- 2012-11-30 WO PCT/EP2012/074092 patent/WO2013120553A1/en not_active Ceased
- 2012-11-30 CN CN201810059151.2A patent/CN108103069B/zh active Active
- 2012-11-30 JP JP2014556934A patent/JP6411218B2/ja active Active
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- 2012-11-30 HU HUE12794962A patent/HUE036955T2/hu unknown
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- 2012-11-30 EP EP12794962.6A patent/EP2814844B1/en active Active
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-
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- 2015-02-26 US US14/632,079 patent/US20150274825A1/en not_active Abandoned
-
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- 2017-10-17 CY CY20171101082T patent/CY1120068T1/el unknown
-
2018
- 2018-09-26 JP JP2018180187A patent/JP6740308B2/ja active Active
Non-Patent Citations (1)
| Title |
|---|
| Arts RJW et al., "TREM-1 interaction with the LPS/TLR4 receptor complex", Eur. Cytokine Netw., vol.22, no.1, p.11-14, 2011/03 EMBL: UniProtKB - Q9NP99 (TREM1_HUMAN)(公開日:2000/10/1) * |
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| CN108103069A (zh) | 2018-06-01 |
| EP3611190A1 (en) | 2020-02-19 |
| JP6740308B2 (ja) | 2020-08-12 |
| US20150274825A1 (en) | 2015-10-01 |
| PL2814844T3 (pl) | 2017-12-29 |
| EP3196214B1 (en) | 2019-07-31 |
| CY1120068T1 (el) | 2018-12-12 |
| NO2814844T3 (cg-RX-API-DMAC7.html) | 2017-12-30 |
| CN104220456B (zh) | 2018-02-23 |
| TW201335186A (zh) | 2013-09-01 |
| DK2814844T3 (da) | 2017-11-13 |
| US9000127B2 (en) | 2015-04-07 |
| EP2814844B1 (en) | 2017-08-02 |
| EP2814844A1 (en) | 2014-12-24 |
| SMT201700488T1 (it) | 2017-11-15 |
| SI2814844T1 (sl) | 2017-10-30 |
| HUE036955T2 (hu) | 2018-08-28 |
| JP2018203777A (ja) | 2018-12-27 |
| RS56593B1 (sr) | 2018-02-28 |
| LT2814844T (lt) | 2017-10-25 |
| JP6411218B2 (ja) | 2018-10-24 |
| CN108103069B (zh) | 2021-08-10 |
| PT2814844T (pt) | 2017-09-18 |
| WO2013120553A1 (en) | 2013-08-22 |
| CN104220456A (zh) | 2014-12-17 |
| ES2640268T3 (es) | 2017-11-02 |
| US20130211050A1 (en) | 2013-08-15 |
| EP3196214A1 (en) | 2017-07-26 |
| HRP20171585T1 (hr) | 2017-12-01 |
| JP2015508762A (ja) | 2015-03-23 |
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