JP2005518332A - 細胞表面のプロテアーゼにより活性化される結合体およびその治療的使用 - Google Patents
細胞表面のプロテアーゼにより活性化される結合体およびその治療的使用 Download PDFInfo
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- Ophthalmology & Optometry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US29326701P | 2001-05-23 | 2001-05-23 | |
PCT/US2002/016819 WO2002095007A2 (en) | 2001-05-23 | 2002-05-23 | Conjugates activated by cell surface proteases and therapeutic uses thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2005518332A true JP2005518332A (ja) | 2005-06-23 |
Family
ID=23128397
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002592470A Withdrawn JP2005518332A (ja) | 2001-05-23 | 2002-05-23 | 細胞表面のプロテアーゼにより活性化される結合体およびその治療的使用 |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1545572A4 (de) |
JP (1) | JP2005518332A (de) |
KR (1) | KR20040004642A (de) |
CA (1) | CA2447023A1 (de) |
WO (1) | WO2002095007A2 (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012023476A1 (ja) | 2010-08-18 | 2012-02-23 | 独立行政法人産業技術総合研究所 | 有機半導体薄膜及び単結晶性有機半導体薄膜の製造方法 |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7037667B1 (en) | 1998-06-01 | 2006-05-02 | Agensys, Inc. | Tumor antigen useful in diagnosis and therapy of prostate and colon cancer |
EP1544304A4 (de) * | 2002-07-31 | 2006-05-10 | Astellas Pharma Inc | Neue serinprotease |
WO2005020897A2 (en) | 2003-08-22 | 2005-03-10 | Dendreon Corporation | Compositions and methods for the treatment of disease associated with trp-p8 expression |
US7947436B2 (en) | 2004-12-13 | 2011-05-24 | Alethia Biotherapeutics Inc. | Polynucleotides and polypeptide sequences involved in the process of bone remodeling |
WO2007047995A2 (en) | 2005-10-21 | 2007-04-26 | Catalyst Biosciences, Inc. | Modified proteases that inhibit complement activation |
DK1986622T3 (da) | 2006-02-15 | 2014-01-13 | Dendreon Corp | Små-molekyle-modulatorer af Trp-p8-aktivitet |
US7772266B2 (en) | 2006-02-15 | 2010-08-10 | Dendreon Corporation | Small-molecule modulators of TRP-P8 activity |
KR100906145B1 (ko) * | 2006-05-30 | 2009-07-03 | 한국생명공학연구원 | Tmprss4 억제제를 유효성분으로 포함하는 항암제 |
KR20140072201A (ko) | 2006-07-05 | 2014-06-12 | 카탈리스트 바이오사이언시즈, 인코포레이티드 | 프로테아제 스크리닝 방법 및 이에 의해 확인된 프로테아제 |
FR2906724B1 (fr) | 2006-10-04 | 2009-03-20 | Sanofi Pasteur Sa | Methode d'immunisation contre les 4 serotypes de la dengue. |
TWI538916B (zh) | 2008-04-11 | 2016-06-21 | 介控生化科技公司 | 經修飾的因子vii多肽和其用途 |
EP2353609A1 (de) | 2010-02-04 | 2011-08-10 | Sanofi Pasteur | Immunisierungszusammensetzungen und -verfahren |
US9869021B2 (en) | 2010-05-25 | 2018-01-16 | Aventa Technologies, Inc. | Showerhead apparatus for a linear batch chemical vapor deposition system |
AR091310A1 (es) | 2012-02-16 | 2015-01-28 | Rqx Pharmaceuticals Inc | Antibioticos de peptidos lineales |
CN104812408A (zh) | 2012-07-24 | 2015-07-29 | 赛诺菲巴斯德有限公司 | 用于防止登革热病毒感染的疫苗组合物 |
EP3932422A1 (de) | 2012-07-24 | 2022-01-05 | Sanofi Pasteur | Impfstoffzusammensetzungen zur vorbeugung von dengue-virus-infektionen |
JP6363600B2 (ja) | 2012-07-25 | 2018-07-25 | カタリスト・バイオサイエンシーズ・インコーポレイテッドCatalyst Biosciences, Inc. | 修飾第x因子ポリペプチドおよびその使用 |
BR112015012515B1 (pt) | 2012-11-30 | 2023-04-11 | Sanofi Pasteur | Uso de antígenos, construções de ácido nucleico ou vetores virais capazes de expressar uma partícula do tipo vírus (vlp) da dengue e de uma vacina contra sarampo, uma vacina contra caxumba e uma vacina contra rubéola |
AU2014249003A1 (en) | 2013-03-13 | 2015-10-15 | Forma Therapeutics, Inc. | Novel compounds and compositions for inhibition of FASN |
RS63143B1 (sr) | 2016-06-01 | 2022-05-31 | Athira Pharma Inc | Jedinjenja |
MX2019015402A (es) | 2017-06-22 | 2020-07-20 | Catalyst Biosciences Inc | Polipeptidos de serina proteasa 1 de tipo membrana modificada (mtsp-1) y metodos de uso. |
TWI767148B (zh) | 2018-10-10 | 2022-06-11 | 美商弗瑪治療公司 | 抑制脂肪酸合成酶(fasn) |
US10793554B2 (en) | 2018-10-29 | 2020-10-06 | Forma Therapeutics, Inc. | Solid forms of 4-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl)benzoyl)piperazin-1-yl)(1-hydroxycyclopropyl)methanone |
WO2021030787A1 (en) | 2019-08-15 | 2021-02-18 | Catalyst Biosciences, Inc. | Modified factor vii polypeptides for subcutaneous administration and on-demand treatment |
EP3932935A1 (de) * | 2020-06-29 | 2022-01-05 | Centre National de la Recherche Scientifique | Antibakterielle peptide |
WO2024150172A1 (en) * | 2023-01-11 | 2024-07-18 | Bright Peak Therapeutics Ag | Cleavable peptides and methods of use thereof |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5972616A (en) * | 1998-02-20 | 1999-10-26 | The Board Of Trustees Of The University Of Arkansas | TADG-15: an extracellular serine protease overexpressed in breast and ovarian carcinomas |
CA2362670A1 (en) * | 1999-03-12 | 2000-09-14 | Georgetown University | Matriptase, a serine protease and its applications |
AU784746B2 (en) * | 1999-11-18 | 2006-06-08 | Dendreon Corporation | Nucleic acids encoding endotheliases, endotheliases and uses thereof |
MXPA02009019A (es) * | 2000-03-15 | 2003-02-12 | Du Pont Pharm Co | Farmacos antineoplasticos de objetivo, que se desdoblan por la peptidasa y su uso terapeutico. |
WO2003000201A2 (en) * | 2001-06-25 | 2003-01-03 | Drug Innovation & Design, Incorporated | Exponential pattern recognition based cellular targeting, compositions, methods and anticancer applications |
WO2003037326A1 (en) * | 2001-10-29 | 2003-05-08 | Corvas International, Inc. | Solid phase synthesis of chemical libraries |
CN101044154A (zh) * | 2002-02-14 | 2007-09-26 | 威廉·J·鲁特 | 治疗宿主中切割的嵌合分子 |
AU2003269880A1 (en) * | 2002-05-21 | 2003-12-22 | Dendreon Corporation | Nucleic acid molecules encoding a transmembrane serine protease 12, the encoded polypeptides and methods based thereon |
-
2002
- 2002-05-23 KR KR10-2003-7015240A patent/KR20040004642A/ko not_active Application Discontinuation
- 2002-05-23 CA CA002447023A patent/CA2447023A1/en not_active Abandoned
- 2002-05-23 EP EP02739474A patent/EP1545572A4/de not_active Withdrawn
- 2002-05-23 WO PCT/US2002/016819 patent/WO2002095007A2/en not_active Application Discontinuation
- 2002-05-23 JP JP2002592470A patent/JP2005518332A/ja not_active Withdrawn
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012023476A1 (ja) | 2010-08-18 | 2012-02-23 | 独立行政法人産業技術総合研究所 | 有機半導体薄膜及び単結晶性有機半導体薄膜の製造方法 |
US9059407B2 (en) | 2010-08-18 | 2015-06-16 | National Institute Of Advanced Industrial Science And Technology | Method for manufacturing organic semiconductor thin film and monocryastalline organic semiconductor thin film |
Also Published As
Publication number | Publication date |
---|---|
EP1545572A4 (de) | 2006-04-12 |
WO2002095007A2 (en) | 2002-11-28 |
EP1545572A2 (de) | 2005-06-29 |
WO2002095007A3 (en) | 2005-05-06 |
CA2447023A1 (en) | 2002-11-28 |
KR20040004642A (ko) | 2004-01-13 |
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