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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- 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
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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
- 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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- Hematology (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)
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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) |
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| JP2014502149A JP2014502149A (ja) | 2014-01-30 |
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| JP6100694B2 true JP6100694B2 (ja) | 2017-03-22 |
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| RU2564125C2 (ru) | 2009-12-07 | 2015-09-27 | Пирис Аг | Мутеины липокалина 2 человека (lcn2, hngal) с аффинностью для определенной мишени |
| US9260492B2 (en) | 2010-11-15 | 2016-02-16 | Pieris Ag | Muteins of human lipocalin 2 with affinity for glypican-3 (GPC-3) |
| WO2013174783A1 (en) * | 2012-05-23 | 2013-11-28 | Pieris Ag | Lipocalin muteins with binding-affinity for glypican-3 (gpc-3) and use of lipocalin muteins for target-specific delivery to cells expressing gpc-3 |
| EP2920202B1 (en) | 2012-11-19 | 2018-08-29 | Pieris Pharmaceuticals GmbH | Novel specific-binding polypeptides and uses thereof |
| SG10201912019WA (en) * | 2014-05-22 | 2020-02-27 | Pieris Pharmaceuticals Gmbh | Novel specific-binding polypeptides and uses thereof |
| US11382963B2 (en) * | 2015-01-12 | 2022-07-12 | Pieris Pharmaceuticals Gmbh | Engineered T cells and uses therefor |
| CA2973640A1 (en) | 2015-01-28 | 2016-08-04 | Rachida Siham Bel Aiba | Novel proteins specific for angiogenesis |
| BR112017020434A2 (pt) | 2015-05-04 | 2018-06-26 | Pieris Pharmaceuticals Gmbh | polipeptídeos de fusão, molécula de ácido nucleico, célula hospedeira, método para produzir um polipeptídeo de fusão, usos do polipeptídeo de fusão, métodos para ativar as vias de sinalização, para coestimular células, para induzir a proliferação de linfócitos t, para direcionar o agrupamento de cd137, para induzir uma resposta local de células t, para induzir uma resposta local de células nk e para induzir a produção de il-2 |
| DK3292137T3 (da) | 2015-05-04 | 2022-10-17 | Pieris Pharmaceuticals Gmbh | Proteiner specifikke for cd137 |
| MX390894B (es) | 2015-05-18 | 2025-03-21 | Pieris Pharmaceuticals Gmbh | Polipéptido de fusión anti-cáncer. |
| KR20180008649A (ko) * | 2015-05-18 | 2018-01-24 | 피어이스 파마슈티컬즈 게엠베하 | 글리피칸-3(gpc3)에 대해 친화도를 갖는 인간 리포칼린 2의 뮤테인 |
| EP3115066A1 (en) * | 2015-07-07 | 2017-01-11 | Technische Universität München | Novel psma-specific binding proteins |
| KR102818445B1 (ko) * | 2015-09-23 | 2025-06-10 | 브리스톨-마이어스 스큅 컴퍼니 | 글리피칸-3-결합 피브로넥틴 기반 스캐폴드 분자 |
| EA035586B1 (ru) | 2015-11-30 | 2020-07-10 | Пиерис Острелиа Пти Лтд. | Новые антиангиогенные слитые белки |
| 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 |
| EP3503930B1 (en) | 2016-08-29 | 2024-12-11 | Fred Hutchinson Cancer Center | Chelating platform for delivery of radionuclides |
| CN111542535A (zh) | 2017-12-20 | 2020-08-14 | 圣安娜儿童癌症研究中心 | 配体调控的蛋白-蛋白相互作用系统 |
| EP3502130A1 (en) | 2017-12-20 | 2019-06-26 | St. Anna Kinderkrebsforschung | Ligand regulated protein-protein interaction system |
| KR20210080460A (ko) | 2018-10-23 | 2021-06-30 | 드래곤플라이 쎄라퓨틱스, 인크. | 이종이량체성 Fc-융합된 단백질 |
| CA3127973A1 (en) * | 2019-03-29 | 2020-10-08 | Pieris Pharmaceuticals Gmbh | Inhaled administration of lipocalin muteins |
| AU2021260960A1 (en) | 2020-04-22 | 2022-11-24 | Dragonfly Therapeutics, Inc. | Formulation, dosage regimen, and manufacturing process for heterodimeric Fc-fused proteins |
| AU2021285201A1 (en) | 2020-06-05 | 2022-11-24 | Pieris Pharmaceuticals Gmbh | Multimeric immunomodulator targeting 4-1BB |
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 |
| KR20010052622A (ko) | 1998-06-08 | 2001-06-25 | 프리돌린 클라우스너, 롤란드 비. 보레르 | 만성 씨형 간염을 치료하기 위한 폴리에틸렌글리콜-인터페론-알파 및 리바비린의 용도 |
| 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 |
| WO2002024866A2 (en) * | 2000-09-21 | 2002-03-28 | University Of Massachusetts | Method of inducing apoptosis in lymphoid cells |
| US7211395B2 (en) | 2001-03-09 | 2007-05-01 | Dyax Corp. | Serum albumin binding moieties |
| AU2001298053A1 (en) | 2001-09-27 | 2003-04-14 | 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 |
| AU2003275958A1 (en) | 2003-08-25 | 2005-03-10 | Pieris Proteolab Ag | Muteins of tear lipocalin |
| US7892827B2 (en) | 2004-11-26 | 2011-02-22 | Pieris Ag | Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4) |
| WO2007038619A2 (en) | 2005-09-27 | 2007-04-05 | Amunix, Inc. | 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 |
| WO2009012394A1 (en) | 2007-07-17 | 2009-01-22 | Medarex, Inc. | Monoclonal antibodies against glypican-3 |
| US8420051B2 (en) * | 2008-06-24 | 2013-04-16 | Technische Universitaet Meunchen | Muteins of hNGAL and related proteins with affinity for a given target |
| US9260492B2 (en) | 2010-11-15 | 2016-02-16 | Pieris Ag | Muteins of human lipocalin 2 with affinity for glypican-3 (GPC-3) |
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| US9260492B2 (en) | 2016-02-16 |
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