NO331690B1 - Forbindelse, og farmasoytisk kombinasjon av forbindelse, som har en aktivitet til a modulere signaloverforing formidlet av AILIM for forsterkning av virkningen av immunsupprimerende midler pa undertrykkelse, behandling eller forebyggelse av transplantatavstotning ved transplantasjon av et organ, del av et organ eller et vev. - Google Patents
Forbindelse, og farmasoytisk kombinasjon av forbindelse, som har en aktivitet til a modulere signaloverforing formidlet av AILIM for forsterkning av virkningen av immunsupprimerende midler pa undertrykkelse, behandling eller forebyggelse av transplantatavstotning ved transplantasjon av et organ, del av et organ eller et vev. Download PDFInfo
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- NO331690B1 NO331690B1 NO20033839A NO20033839A NO331690B1 NO 331690 B1 NO331690 B1 NO 331690B1 NO 20033839 A NO20033839 A NO 20033839A NO 20033839 A NO20033839 A NO 20033839A NO 331690 B1 NO331690 B1 NO 331690B1
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- ailim
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
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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
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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
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
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- Immunology (AREA)
- Organic Chemistry (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Surgery (AREA)
- Microbiology (AREA)
- Mycology (AREA)
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- Transplantation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Graft Or Block Polymers (AREA)
- External Artificial Organs (AREA)
- Cylinder Crankcases Of Internal Combustion Engines (AREA)
- Transplanting Machines (AREA)
- Soil Working Implements (AREA)
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JP2001056216 | 2001-03-01 | ||
JP2001056209 | 2001-03-01 | ||
JP2002008028 | 2002-01-16 | ||
PCT/JP2002/000930 WO2002070010A1 (fr) | 2001-03-01 | 2002-02-05 | Inhibiteurs de rejet du greffon |
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NO20033839D0 NO20033839D0 (no) | 2003-08-29 |
NO20033839L NO20033839L (no) | 2003-11-03 |
NO331690B1 true NO331690B1 (no) | 2012-02-27 |
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NO20033839A NO331690B1 (no) | 2001-03-01 | 2003-08-29 | Forbindelse, og farmasoytisk kombinasjon av forbindelse, som har en aktivitet til a modulere signaloverforing formidlet av AILIM for forsterkning av virkningen av immunsupprimerende midler pa undertrykkelse, behandling eller forebyggelse av transplantatavstotning ved transplantasjon av et organ, del av et organ eller et vev. |
NO20110218A NO20110218L (no) | 2001-03-01 | 2011-02-08 | Transplantatrejeksjonssuppressorer |
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NO20110218A NO20110218L (no) | 2001-03-01 | 2011-02-08 | Transplantatrejeksjonssuppressorer |
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EP (2) | EP1769807B1 (sk) |
JP (1) | JP4212278B2 (sk) |
KR (1) | KR100609444B1 (sk) |
CN (1) | CN1518458B (sk) |
AT (2) | ATE352318T1 (sk) |
AU (1) | AU2002228435B2 (sk) |
BR (1) | BR0207787A (sk) |
CA (1) | CA2439858C (sk) |
CY (1) | CY1110143T1 (sk) |
CZ (1) | CZ20032406A3 (sk) |
DE (2) | DE60235928D1 (sk) |
DK (1) | DK1769807T3 (sk) |
ES (1) | ES2344219T3 (sk) |
HK (2) | HK1061531A1 (sk) |
HU (2) | HU228045B1 (sk) |
IL (2) | IL156845A0 (sk) |
MX (1) | MXPA03006736A (sk) |
NO (2) | NO331690B1 (sk) |
NZ (1) | NZ527076A (sk) |
PT (1) | PT1769807E (sk) |
RU (1) | RU2263512C2 (sk) |
SI (1) | SI1769807T1 (sk) |
SK (1) | SK288048B6 (sk) |
WO (1) | WO2002070010A1 (sk) |
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Publication number | Priority date | Publication date | Assignee | Title |
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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 |
US7112655B1 (en) | 1997-02-27 | 2006-09-26 | Japan Tobacco, Inc. | JTT-1 protein and methods of inhibiting lymphocyte activation |
DE19821060A1 (de) * | 1997-09-23 | 1999-04-15 | Bundesrepublik Deutschland Let | Ko-stimulierendes Polypeptid von T-Zellen, monoklonale Antikörper sowie die Herstellung und deren Verwendung |
JP3871503B2 (ja) | 1999-08-30 | 2007-01-24 | 日本たばこ産業株式会社 | 免疫性疾患治療剤 |
JP4210454B2 (ja) | 2001-03-27 | 2009-01-21 | 日本たばこ産業株式会社 | 炎症性腸疾患治療剤 |
CN1411373A (zh) * | 1999-12-16 | 2003-04-16 | 特瓦制药工业有限公司 | 制备来氟米特的新方法和新晶形的来氟米特 |
JP3597140B2 (ja) | 2000-05-18 | 2004-12-02 | 日本たばこ産業株式会社 | 副刺激伝達分子ailimに対するヒトモノクローナル抗体及びその医薬用途 |
JP4212278B2 (ja) | 2001-03-01 | 2009-01-21 | 日本たばこ産業株式会社 | 移植片拒絶反応抑制剤 |
GB0504544D0 (en) * | 2005-03-04 | 2005-04-13 | Novartis Ag | Organic compounds |
JP2006321765A (ja) * | 2005-05-20 | 2006-11-30 | Mikiko Ueda | 肝移植における拒絶反応の予防又は治療薬、或いは拒絶反応とは断定できない肝機能異常の治療薬 |
US20080279851A1 (en) * | 2007-05-07 | 2008-11-13 | Medlmmune, Llc | Anti-icos antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
US9931386B2 (en) * | 2008-06-16 | 2018-04-03 | Atsuo Ochi | Recombinant multiple domain fusion protein mitogens and use thereof for inducing enhancement or repression of antigen-specific immunity |
EP2455396A4 (en) * | 2009-07-16 | 2013-05-01 | Otsuka Chemical Co Ltd | EXTRACELLULAR AILIM DOMAIN PLACED WITH SUGAR CHAINS AND METHOD OF MANUFACTURING THE SAME |
US9420770B2 (en) | 2009-12-01 | 2016-08-23 | Indiana University Research & Technology Corporation | Methods of modulating thrombocytopenia and modified transgenic pigs |
WO2011130322A1 (en) * | 2010-04-12 | 2011-10-20 | University Of Miami | Macroporous bioengineered scaffolds for cell transplantation |
RU2456615C1 (ru) * | 2011-03-25 | 2012-07-20 | Федеральное государственное учреждение "Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова" Министерства здравоохранения и социального развития Российской Федерации | Способ профилактики отторжения трансплантата трупной почки |
BR112013025045B1 (pt) | 2011-03-31 | 2020-10-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | anticorpos direcionados contra icos e usos dos mesmos |
US20150139994A1 (en) * | 2013-11-12 | 2015-05-21 | The Regents Of The University Of California | Compositions and methods for preventing allogeneic immune rejection |
KR102312817B1 (ko) * | 2013-11-22 | 2021-10-13 | 다케다 야쿠힌 고교 가부시키가이샤 | C1-에스테라제 억제제를 사용한 장기 이식 환자에서의 항체-매개성 거부반응의 치료 방법 |
GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
CA2942384C (en) | 2014-03-12 | 2024-01-23 | Icahn School Of Medicine At Mount Sinai | Method for identifying kidney allograft recipients at risk for chronic injury |
ES2897004T3 (es) * | 2014-06-26 | 2022-02-28 | Icahn School Med Mount Sinai | Métodos para diagnosticar el riesgo de fibrosis y rechazo de aloinjerto renal |
ES2850281T3 (es) | 2014-06-26 | 2021-08-26 | Icahn School Med Mount Sinai | Método para diagnosticar el rechazo agudo subclínico y clínico mediante el análisis de conjuntos de genes predictivos, un agente terapéutico para usar en el tratamiento y kits para determinar la expresión |
MA41414A (fr) | 2015-01-28 | 2017-12-05 | Centre Nat Rech Scient | Protéines de liaison agonistes d' icos |
PE20181297A1 (es) | 2015-12-03 | 2018-08-07 | Glaxosmithkline Ip Dev Ltd | Dinucleotidos de purino ciclico como moduladores de sting |
WO2017098421A1 (en) | 2015-12-08 | 2017-06-15 | Glaxosmithkline Intellectual Property Development Limited | Benzothiadiazine compounds |
WO2017153952A1 (en) | 2016-03-10 | 2017-09-14 | Glaxosmithkline Intellectual Property Development Limited | 5-sulfamoyl-2-hydroxybenzamide derivatives |
WO2017175156A1 (en) | 2016-04-07 | 2017-10-12 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides useful as protein modulators |
IL285702B (en) | 2016-04-07 | 2022-09-01 | Glaxosmithkline Ip Dev Ltd | Heterocyclic amides are useful as protein modulators |
AU2017260854B2 (en) | 2016-05-05 | 2020-01-30 | Glaxosmithkline Intellectual Property (No.2) Limited | Enhancer of Zeste Homolog 2 inhibitors |
US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
WO2018029474A2 (en) | 2016-08-09 | 2018-02-15 | Kymab Limited | Anti-icos antibodies |
KR102531889B1 (ko) | 2016-06-20 | 2023-05-17 | 키맵 리미티드 | 항-pd-l1 및 il-2 사이토카인 |
JP2019521166A (ja) | 2016-07-20 | 2019-07-25 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | Perk阻害剤としてのイソキノリン誘導体 |
KR20230044038A (ko) | 2016-08-09 | 2023-03-31 | 키맵 리미티드 | 항-icos 항체 |
EP3534947A1 (en) | 2016-11-03 | 2019-09-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
BR112019017738A2 (pt) | 2017-02-27 | 2020-04-07 | Glaxosmithkline Ip Dev Ltd | combinação, composição farmacêutica, uso de uma combinação ou composição farmacêutica, método para tratar câncer em um humano, e, composto |
JP2020522555A (ja) | 2017-06-09 | 2020-07-30 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | 組み合わせ療法 |
CN110831971A (zh) | 2017-06-09 | 2020-02-21 | 葛兰素史克知识产权开发有限公司 | 用icos激动剂和ox40激动剂治疗癌症的组合疗法 |
CN110709423A (zh) | 2017-06-09 | 2020-01-17 | 葛兰素史克知识产权开发有限公司 | 用icos激动剂和ox40激动剂治疗癌症的组合疗法 |
GB201709808D0 (en) | 2017-06-20 | 2017-08-02 | Kymab Ltd | Antibodies |
WO2019021208A1 (en) | 2017-07-27 | 2019-01-31 | Glaxosmithkline Intellectual Property Development Limited | USEFUL INDAZOLE DERIVATIVES AS PERK INHIBITORS |
WO2019053617A1 (en) | 2017-09-12 | 2019-03-21 | Glaxosmithkline Intellectual Property Development Limited | CHEMICAL COMPOUNDS |
WO2019053613A2 (en) | 2017-09-14 | 2019-03-21 | Glaxosmithkline Intellectual Property Development Limited | POLY THERAPY FOR THE TREATMENT OF CANCER |
BR112020006780A2 (pt) | 2017-10-05 | 2020-10-06 | Glaxosmithkline Intellectual Property Development Limited | moduladores do estimulador de genes do interferon (sting) |
TW201927771A (zh) | 2017-10-05 | 2019-07-16 | 英商葛蘭素史密斯克藍智慧財產發展有限公司 | 可作為蛋白質調節劑之雜環醯胺及其使用方法 |
WO2019122882A1 (en) | 2017-12-19 | 2019-06-27 | Kymab Limited | Bispecific antibody for icos and pd-l1 |
GB201721338D0 (en) | 2017-12-19 | 2018-01-31 | Kymab Ltd | Anti-icos Antibodies |
RU2688172C1 (ru) * | 2018-04-05 | 2019-05-20 | Государственное бюджетное учреждение здравоохранения Московской области "Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского" (ГБУЗ МО МОНИКИ им. М.Ф. Владимирского) | Способ профилактики отторжения трансплантата трупной почки |
CA3095198A1 (en) | 2018-04-16 | 2019-10-24 | Icahn School Of Medicine At Mount Sinai | Method and kits for prediction of acute rejection and renal allograft loss using pre-transplant transcriptomic signatures in recipient blood |
GB201807924D0 (en) | 2018-05-16 | 2018-06-27 | Ctxt Pty Ltd | Compounds |
US20210260033A1 (en) | 2018-05-31 | 2021-08-26 | Glaxosmithkline Intellectual Property Development Limited | Combined therapy with icos binding proteins and argininemethyltransferase inhibitors |
CA3101553A1 (en) | 2018-05-31 | 2019-12-05 | Glaxosmithkline Intellectual Property Development Limited | Combination of a type ii protein arginine methyltransferase inhibitor and an icos binding protein to treat cancer |
WO2020031087A1 (en) | 2018-08-06 | 2020-02-13 | Glaxosmithkline Intellectual Property Development Limited | Combination therapy |
MX2021004603A (es) | 2018-10-22 | 2021-09-08 | Glaxosmithkline Ip Dev Ltd | Dosificacion. |
US20200368369A1 (en) * | 2019-05-22 | 2020-11-26 | Wyvern Pharmaceuticals Inc. | Composition for endogenous production of checkpoint protein precursors |
GB201910304D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
GB201910305D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
WO2021018941A1 (en) | 2019-07-31 | 2021-02-04 | Glaxosmithkline Intellectual Property Development Limited | Methods of treating cancer |
WO2021043961A1 (en) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Dosing regimen for the treatment of cancer with an anti icos agonistic antibody and chemotherapy |
WO2021046289A1 (en) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Dosing regimen for the treatment of cancer with an anti icos agonistic antibody and ipilimumab |
AU2020355614A1 (en) | 2019-09-27 | 2022-04-14 | Glaxosmithkline Intellectual Property Development Limited | Antigen binding proteins |
CN113294813B (zh) * | 2020-02-24 | 2022-09-02 | 宁波方太厨具有限公司 | 一种电磁灶 |
JP2023521227A (ja) | 2020-04-14 | 2023-05-23 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | 癌の併用療法 |
JP2023521465A (ja) | 2020-04-14 | 2023-05-24 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | ICOS抗体とPD-L1抗体TGF-β-受容体融合タンパク質とに基づく癌の併用治療 |
AU2021256652A1 (en) | 2020-04-14 | 2022-11-03 | Glaxosmithkline Intellectual Property Development Limited | Combination treatment for cancer involving anti-ICOS and anti-PD1 antibodies, optionally further involving anti-tim3 antibodies |
GB202007099D0 (en) | 2020-05-14 | 2020-07-01 | Kymab Ltd | Tumour biomarkers for immunotherapy |
KR20230154230A (ko) | 2021-03-02 | 2023-11-07 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | Dnmt1 억제제로서의 치환된 피리딘 |
JP2024511831A (ja) | 2021-03-31 | 2024-03-15 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | 抗原結合タンパク質およびそれらの組み合わせ |
WO2022243378A1 (en) | 2021-05-18 | 2022-11-24 | Kymab Limited | Uses of anti-icos antibodies |
GB202107994D0 (en) | 2021-06-04 | 2021-07-21 | Kymab Ltd | Treatment of cancer |
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Family Cites Families (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5506126A (en) * | 1988-02-25 | 1996-04-09 | The General Hospital Corporation | Rapid immunoselection cloning method |
US6075181A (en) * | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US5521288A (en) * | 1990-03-26 | 1996-05-28 | Bristol-Myers Squibb Company | CD28IG fusion protein |
US5770197A (en) * | 1991-06-27 | 1998-06-23 | Bristol-Myers Squibb Company | Methods for regulating the immune response using B7 binding molecules and IL4-binding molecules |
JP3162438B2 (ja) | 1991-09-12 | 2001-04-25 | 住友製薬株式会社 | 高感度特異的抗体測定法 |
US5484892A (en) * | 1993-05-21 | 1996-01-16 | Dana-Farber Cancer Institute, Inc. | Monoclonal antibodies that block ligand binding to the CD22 receptor in mature B cells |
US6719972B1 (en) * | 1994-06-03 | 2004-04-13 | Repligen Corporation | Methods of inhibiting T cell proliferation or IL-2 accumulation with CTLA4- specific antibodies |
US5747461A (en) * | 1994-07-26 | 1998-05-05 | Markov; Angel K. | Synergistic administration of cyclosporine and fructose diphosphate |
WO1997026912A2 (en) | 1996-01-23 | 1997-07-31 | Genentech, Inc. | Anti-cd18 antibodies for use against stroke |
US5914112A (en) * | 1996-01-23 | 1999-06-22 | Genentech, Inc. | Anti-CD18 antibodies in stroke |
WO1998011909A1 (en) | 1996-09-18 | 1998-03-26 | Zetesis S.P.A. | Use of proteins as agents against autoimmune diseases |
EP1007090B1 (en) * | 1996-11-08 | 2009-12-30 | Biogen Idec Inc. | Identification of unique binding interactions between certain antibodies and the human b7.1 (cd80) and b7.2 (cd28) co-stimulatory antigens |
AU4145597A (en) | 1997-02-20 | 1998-09-09 | Cedars-Sinai Medical Center | Ulcerative colitis panca secretory vesicle antigen and methods of using sa me |
FI107538B (fi) * | 1997-02-26 | 2001-08-31 | Raisio Benecol Oy | Menetelmä stanoliesterien valmistamiseksi |
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 |
US7112655B1 (en) * | 1997-02-27 | 2006-09-26 | Japan Tobacco, Inc. | JTT-1 protein and methods of inhibiting lymphocyte activation |
DE122007000021I1 (de) | 1997-04-07 | 2007-05-24 | Genentech Inc | Anti-vefg Antibodies |
DE19821060A1 (de) | 1997-09-23 | 1999-04-15 | Bundesrepublik Deutschland Let | Ko-stimulierendes Polypeptid von T-Zellen, monoklonale Antikörper sowie die Herstellung und deren Verwendung |
CA2305350C (en) * | 1997-09-23 | 2015-04-07 | Bundesrepublik Deutschland Letztvertreten Durch Den Direktor Des Robert-Koch-Instituts | Costimulating polypeptide of t cells, monoclonal antibodies, and the preparation and use thereof |
JPH11228442A (ja) * | 1998-02-09 | 1999-08-24 | Cypros Pharmaceut Corp | 臓器移植後のシクロスポリン投与量を低減するためのフルクトース二リン酸の使用 |
AU767241B2 (en) * | 1998-09-14 | 2003-11-06 | Qiang Xu | Immunosuppressive agents |
JP2000154151A (ja) * | 1998-09-14 | 2000-06-06 | Kyo Jo | 免疫抑制剤 |
AU1102000A (en) * | 1998-10-07 | 2000-04-26 | Millennium Pharmaceuticals, Inc. | Novel th2-specific molecules and uses thereof |
SI1149114T1 (sl) * | 1999-02-03 | 2014-08-29 | Amgen Inc. | Polipeptidi, vkljuäśeni v imunskem odgovoru |
EP1181053A2 (en) | 1999-05-06 | 2002-02-27 | Genetics Institute, Inc. | Use of soluble costimulatory molecules to enhance immune responses |
AU6615500A (en) | 1999-07-28 | 2001-02-19 | Genetics Institute Inc. | Preventing immune-mediated abortion by inhibiting costimulation |
WO2001012658A2 (en) | 1999-08-11 | 2001-02-22 | Isis Innovations Limited | Human icos ligand and application thereof |
JP4210454B2 (ja) | 2001-03-27 | 2009-01-21 | 日本たばこ産業株式会社 | 炎症性腸疾患治療剤 |
JP3871503B2 (ja) * | 1999-08-30 | 2007-01-24 | 日本たばこ産業株式会社 | 免疫性疾患治療剤 |
AU7099200A (en) | 1999-09-03 | 2001-04-10 | Human Genome Sciences, Inc. | 52 human secreted proteins |
ES2290052T3 (es) | 1999-09-21 | 2008-02-16 | Genetics Institute, Llc | Moleculas gl50 y usos para las mismas. |
JP2003528586A (ja) | 1999-10-29 | 2003-09-30 | ヒューマン ジノーム サイエンシーズ, インコーポレイテッド | 32個のヒト分泌タンパク質 |
WO2001064704A1 (en) | 2000-03-02 | 2001-09-07 | Mayo Foundation For Medical Education And Research | hB7-H2, A NOVEL CO-STIMULATORY MOLECULE |
JP3597140B2 (ja) * | 2000-05-18 | 2004-12-02 | 日本たばこ産業株式会社 | 副刺激伝達分子ailimに対するヒトモノクローナル抗体及びその医薬用途 |
MXPA03004578A (es) | 2000-11-28 | 2004-05-05 | Amgen Inc | Nuevos polipeptidos involucrados en respuesta inmune. |
JP4212278B2 (ja) | 2001-03-01 | 2009-01-21 | 日本たばこ産業株式会社 | 移植片拒絶反応抑制剤 |
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