JP6100694B2 - グリピカン−３（ｇｐｃ３）に対して親和性を有するヒトリポカリン２の突然変異タンパク質 - Google Patents
グリピカン−３（ｇｐｃ３）に対して親和性を有するヒトリポカリン２の突然変異タンパク質 Download PDFInfo
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- A61P35/00—Antineoplastic agents
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4725—Proteoglycans, e.g. aggreccan
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Oncology (AREA)
- Hematology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US41370610P | 2010-11-15 | 2010-11-15 | |
| EP10191228.5 | 2010-11-15 | ||
| EP10191228 | 2010-11-15 | ||
| US61/413,706 | 2010-11-15 | ||
| PCT/EP2011/070119 WO2012065978A1 (en) | 2010-11-15 | 2011-11-15 | Muteins of human lipocalin 2 with affinity for glypican-3 (gpc3) |
Publications (3)
| Publication Number | Publication Date |
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| JP2014502149A JP2014502149A (ja) | 2014-01-30 |
| JP2014502149A5 JP2014502149A5 (OSRAM) | 2015-01-08 |
| JP6100694B2 true JP6100694B2 (ja) | 2017-03-22 |
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| JP2013538232A Expired - Fee Related JP6100694B2 (ja) | 2010-11-15 | 2011-11-15 | グリピカン−３（ｇｐｃ３）に対して親和性を有するヒトリポカリン２の突然変異タンパク質 |
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| EP (1) | EP2640740B1 (OSRAM) |
| JP (1) | JP6100694B2 (OSRAM) |
| AU (1) | AU2011331232B2 (OSRAM) |
| CA (1) | CA2817779C (OSRAM) |
| DK (1) | DK2640740T3 (OSRAM) |
| WO (1) | WO2012065978A1 (OSRAM) |
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| US9549968B2 (en) * | 2009-12-07 | 2017-01-24 | Pieris Pharmaceuticals Gmbh | Muteins of human lipocalin 2 (LcnC,hNGAL) with affinity for a given target |
| DK2640740T3 (en) | 2010-11-15 | 2017-06-26 | Pieris Pharmaceuticals Gmbh | MUTEINS OF HUMAN LIPOCALIN 2 WITH AFFINITY FOR GLYPICAN-3 (GPC3) |
| US9522940B2 (en) * | 2012-05-23 | 2016-12-20 | Pieris Pharmaceuticals Gmbh | Lipocalin muteins with binding-affinity for glypican-3 (GPC-3) and use of lipocalin muteins for target-specific delivery to cells expressing GPC-3 |
| CA2891557A1 (en) | 2013-03-26 | 2014-05-22 | Pieris Ag | Novel specific-binding polypeptides and uses thereof |
| CN113621050A (zh) * | 2014-05-22 | 2021-11-09 | 皮里斯制药有限公司 | 新型特异性结合多肽及其用途 |
| US11382963B2 (en) * | 2015-01-12 | 2022-07-12 | Pieris Pharmaceuticals Gmbh | Engineered T cells and uses therefor |
| SG10201906859PA (en) | 2015-01-28 | 2019-08-27 | Pieris Pharmaceuticals Gmbh | Novel proteins specific for angiogenesis |
| US11261221B2 (en) | 2015-05-04 | 2022-03-01 | Pieris Pharmaceuticals Gmbh | Proteins specific for CD137 |
| CN107636014B (zh) | 2015-05-04 | 2021-12-07 | 皮里斯制药有限公司 | 抗癌融合多肽 |
| FI3298030T3 (fi) | 2015-05-18 | 2023-02-22 | Pieris Pharmaceuticals Gmbh | Syöpää ehkäisevä fuusiopolypeptidi |
| CN107787327B (zh) * | 2015-05-18 | 2022-02-08 | 皮里斯制药有限公司 | 对磷脂酰肌醇聚糖-3（gpc3）具有亲和力的人脂质运载蛋白2的突变蛋白 |
| EP3115066A1 (en) * | 2015-07-07 | 2017-01-11 | Technische Universität München | Novel psma-specific binding proteins |
| ES2809125T3 (es) * | 2015-09-23 | 2021-03-03 | Bristol Myers Squibb Co | Moléculas de armazón a base de fibronectina de unión a glipicano-3 |
| SG11201803732PA (en) | 2015-11-30 | 2018-06-28 | Pieris Australia Pty Ltd | Novel anti-angiogenic fusion polypeptides |
| TW201725212A (zh) | 2015-12-10 | 2017-07-16 | 第一三共股份有限公司 | 特異性於降鈣素基因相關胜肽的新穎蛋白 |
| ES3015117T3 (en) | 2016-08-29 | 2025-04-29 | Fred Hutchinson Cancer Center | Chelating platform for delivery of radionuclides |
| JP2021506329A (ja) | 2017-12-20 | 2021-02-22 | ザンクト アンナ キンダークレプスフォルシュング | リガンド制御したタンパク質−タンパク質相互作用システム |
| EP3502130A1 (en) | 2017-12-20 | 2019-06-26 | St. Anna Kinderkrebsforschung | Ligand regulated protein-protein interaction system |
| AU2019366956B2 (en) | 2018-10-23 | 2025-10-30 | Dragonfly Therapeutics, Inc. | Heterodimeric Fc-fused proteins |
| CN113939307A (zh) * | 2019-03-29 | 2022-01-14 | 皮里斯制药有限公司 | 脂质运载蛋白突变蛋白的吸入施用 |
| IL297495A (en) | 2020-04-22 | 2022-12-01 | Dragonfly Therapeutics Inc | Dosing regimen, formulation and manufacturing process for fc fusion heterodimeric proteins |
| CN116249709A (zh) | 2020-06-05 | 2023-06-09 | 皮里斯制药有限公司 | 靶向4-1bb的多聚体免疫调节剂 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01215289A (ja) | 1988-02-22 | 1989-08-29 | Toa Nenryo Kogyo Kk | 遺伝子組換えによる正常ヒト血清アルブミンａの製造方法 |
| FR2649991B2 (fr) | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| US5728553A (en) | 1992-09-23 | 1998-03-17 | Delta Biotechnology Limited | High purity albumin and method of producing |
| US5908621A (en) | 1995-11-02 | 1999-06-01 | Schering Corporation | Polyethylene glycol modified interferon therapy |
| US6620413B1 (en) | 1995-12-27 | 2003-09-16 | Genentech, Inc. | OB protein-polymer chimeras |
| DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
| GB9722131D0 (en) | 1997-10-20 | 1997-12-17 | Medical Res Council | Method |
| CA2233725A1 (en) | 1998-03-31 | 1999-09-30 | Hemosol Inc. | Hemoglobin-hydroxyethyl starch complexes |
| PL192364B1 (pl) | 1998-06-08 | 2006-10-31 | Hoffmann La Roche | Zastosowanie koniugatu PEG-IFN-α 2A w połączeniu z rybawiryną |
| US6403564B1 (en) | 1998-10-16 | 2002-06-11 | Schering Corporation | Ribavirin-interferon alfa combination therapy for eradicating detectable HCV-RNA in patients having chronic hepatitis C infection |
| DE19926068C1 (de) | 1999-06-08 | 2001-01-11 | Arne Skerra | Muteine des Bilin-Bindungsproteins |
| US7235520B2 (en) * | 2000-09-21 | 2007-06-26 | University Of Massachusetts | Method of inducing apoptosis in lymphoid cells |
| CA2440582A1 (en) | 2001-03-09 | 2002-10-03 | Dyax Corp. | Serum albumin binding moieties |
| EP1430136A1 (en) | 2001-09-27 | 2004-06-23 | Pieris ProteoLab AG | Muteins of apolipoprotein d |
| WO2003029462A1 (en) | 2001-09-27 | 2003-04-10 | Pieris Proteolab Ag | Muteins of human neutrophil gelatinase-associated lipocalin and related proteins |
| US7691970B2 (en) | 2003-08-25 | 2010-04-06 | Pieris Ag | Muteins of a bilin-binding protein with affinity for a given target |
| WO2005019255A1 (en) | 2003-08-25 | 2005-03-03 | Pieris Proteolab Ag | Muteins of tear lipocalin |
| EP2899277A1 (en) * | 2004-11-26 | 2015-07-29 | Pieris AG | Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4) |
| US20070212703A1 (en) | 2005-09-27 | 2007-09-13 | Stemmer Willem P | Proteinaceous pharmaceuticals and uses thereof |
| US20070087005A1 (en) | 2005-10-14 | 2007-04-19 | Lazar Gregory A | Anti-glypican-3 antibody |
| WO2007137170A2 (en) | 2006-05-20 | 2007-11-29 | Seattle Genetics, Inc. | Anti-glypican-3 antibody drug conjugates |
| RS54624B1 (sr) | 2007-07-17 | 2016-08-31 | E. R. Squibb & Sons, L.L.C. | Monoklonska antitela protiv glipikana-3 |
| EP2313430B1 (en) * | 2008-06-24 | 2018-05-02 | Technische Universität München | Muteins of hngal and related proteins with affinity for a given target |
| DK2640740T3 (en) | 2010-11-15 | 2017-06-26 | Pieris Pharmaceuticals Gmbh | MUTEINS OF HUMAN LIPOCALIN 2 WITH AFFINITY FOR GLYPICAN-3 (GPC3) |
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| US9260492B2 (en) | 2016-02-16 |
| EP2640740B1 (en) | 2017-03-15 |
| US20130296258A1 (en) | 2013-11-07 |
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