JP2001503643A - アスパラギン酸プロテアーゼの一種であるナプシンのクローニングおよび特徴付け - Google Patents
アスパラギン酸プロテアーゼの一種であるナプシンのクローニングおよび特徴付けInfo
- Publication number
- JP2001503643A JP2001503643A JP52398598A JP52398598A JP2001503643A JP 2001503643 A JP2001503643 A JP 2001503643A JP 52398598 A JP52398598 A JP 52398598A JP 52398598 A JP52398598 A JP 52398598A JP 2001503643 A JP2001503643 A JP 2001503643A
- Authority
- JP
- Japan
- Prior art keywords
- napsin
- human
- enzyme
- tissue
- sequence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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Classifications
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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
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6478—Aspartic endopeptidases (3.4.23)
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Molecular Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
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- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3119696P | 1996-11-20 | 1996-11-20 | |
| US4612697P | 1997-05-09 | 1997-05-09 | |
| US60/046,126 | 1997-05-09 | ||
| US60/031,196 | 1997-05-09 | ||
| PCT/US1997/021684 WO1998022597A2 (en) | 1996-11-20 | 1997-11-20 | Cloning and characterization of napsin, an aspartic protease |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007297327A Division JP2008118996A (ja) | 1996-11-20 | 2007-11-15 | アスパラギン酸プロテアーゼの一種であるナプシンのクローニングおよび特徴付け |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001503643A true JP2001503643A (ja) | 2001-03-21 |
| JP2001503643A5 JP2001503643A5 (enExample) | 2005-12-02 |
Family
ID=26706937
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52398598A Withdrawn JP2001503643A (ja) | 1996-11-20 | 1997-11-20 | アスパラギン酸プロテアーゼの一種であるナプシンのクローニングおよび特徴付け |
| JP2007297327A Pending JP2008118996A (ja) | 1996-11-20 | 2007-11-15 | アスパラギン酸プロテアーゼの一種であるナプシンのクローニングおよび特徴付け |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007297327A Pending JP2008118996A (ja) | 1996-11-20 | 2007-11-15 | アスパラギン酸プロテアーゼの一種であるナプシンのクローニングおよび特徴付け |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6225103B1 (enExample) |
| EP (1) | EP0948630B1 (enExample) |
| JP (2) | JP2001503643A (enExample) |
| AT (1) | ATE393227T1 (enExample) |
| AU (1) | AU734220B2 (enExample) |
| CA (1) | CA2271294A1 (enExample) |
| DE (1) | DE69738653T2 (enExample) |
| DK (1) | DK0948630T3 (enExample) |
| ES (1) | ES2308791T3 (enExample) |
| PT (1) | PT948630E (enExample) |
| WO (1) | WO1998022597A2 (enExample) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0897986A3 (en) * | 1997-08-21 | 2000-07-05 | Smithkline Beecham Corporation | Aspartic proteinase 5 (ASP5) |
| US6203979B1 (en) | 1998-01-16 | 2001-03-20 | Incyte Pharmaceuticals, Inc. | Human protease molecules |
| US7045333B1 (en) * | 1998-01-16 | 2006-05-16 | Incyte Corporation | Human protease molecules |
| US6432690B1 (en) * | 1998-01-16 | 2002-08-13 | Incyte Genomics, Inc. | Human aspartic proteases |
| US7160679B1 (en) | 1998-05-21 | 2007-01-09 | Diadexus, Inc. | Method of diagnosing, monitoring, and staging lung cancer |
| CA2303062A1 (en) * | 1998-07-16 | 2000-01-27 | Incyte Pharmaceuticals, Inc. | Human aspartic proteases |
| EP1939297A1 (en) | 1998-09-24 | 2008-07-02 | Pharmacia & Upjohn Company LLC | Alzheimer's disease secretase |
| US7456007B1 (en) | 1998-12-31 | 2008-11-25 | Elan Pharmaceuticals, Inc. | β-secretase enzyme compositions and methods |
| US7115410B1 (en) | 1999-02-10 | 2006-10-03 | Elan Pharmaceuticals, Inc. | β-secretase enzyme compositions and methods |
| NZ534876A (en) | 1999-02-10 | 2006-02-24 | Elan Pharm Inc | Human beta-secretase enzyme, inhibitors and their compositions and uses |
| US7514408B1 (en) | 1999-12-02 | 2009-04-07 | Elan Pharmaceuticals, Inc. | β-secretase enzyme compositions and methods |
| JP2001172200A (ja) * | 1999-12-17 | 2001-06-26 | Meneki Seibutsu Kenkyusho:Kk | ヒトナプシンａに対する抗体およびこれを用いる医薬 |
| ES2275675T3 (es) | 2000-03-23 | 2007-06-16 | Elan Pharmaceuticals, Inc. | Compuestos y metodos para tratar la enfermedad de alzheimer. |
| WO2002000891A2 (en) * | 2000-06-26 | 2002-01-03 | Bayer Aktiengesellschaft | Human napsin-like aspartyl protease |
| EP1666452A2 (en) | 2000-06-30 | 2006-06-07 | Elan Pharmaceuticals, Inc. | Compounds to treat Alzheimer's disease |
| PE20020276A1 (es) | 2000-06-30 | 2002-04-06 | Elan Pharm Inc | COMPUESTOS DE AMINA SUSTITUIDA COMO INHIBIDORES DE ß-SECRETASA PARA EL TRATAMIENTO DE ALZHEIMER |
| ES2252257T3 (es) | 2000-06-30 | 2006-05-16 | Elan Pharmaceuticals, Inc. | Compuestos para tratar la enfermedad de alzheimer. |
| US6846813B2 (en) | 2000-06-30 | 2005-01-25 | Pharmacia & Upjohn Company | Compounds to treat alzheimer's disease |
| EP1500663A1 (en) * | 2000-09-28 | 2005-01-26 | Eli Lilly And Company | Secreted proteins and their uses |
| US7217556B1 (en) | 2000-12-23 | 2007-05-15 | Pfizer Inc | Crystallization and structure determination of glycosylated human beta secretase, an enzyme implicated in Alzheimer's disease |
| US7601528B1 (en) | 2000-12-23 | 2009-10-13 | Elan Pharmaceuticals, Inc. | Crystallization and structure determination of glycosylated human beta secretase, an enzyme implicated in alzheimer's disease |
| US7806980B2 (en) * | 2000-12-23 | 2010-10-05 | Elan Pharmaceuticals, Inc. | Method for crystallizing human beta secretase in complex with an inhibitor |
| US7524668B1 (en) * | 2001-05-10 | 2009-04-28 | Elan Pharmaceuticals, Inc. | Crystal of human beta secretase having monoclinic space group symmetry C2 and methods for crystallization thereof |
| US7384773B1 (en) | 2001-05-10 | 2008-06-10 | Pfizer Inc | Crystal of HIV protease-cleaved human beta secretase and method for crystallization thereof |
| CA2448834A1 (en) | 2001-06-01 | 2002-12-12 | Elan Pharmaceuticals, Inc. | Hydroxy alkyl amine derivatives as beta-secretase inhibitors and their use for the treatment of alzheimer's disease and similar diseases |
| CA2450205A1 (en) | 2001-06-13 | 2002-12-19 | Elan Pharmaceuticals, Inc. | Aminediols for the treatment of alzheimer's disease |
| CA2452039A1 (en) | 2001-06-27 | 2003-01-09 | Elan Pharmaceuticals, Inc. | Beta-hydroxyamine derivatives useful in treatment of alzheimer's disease |
| CA2453451A1 (en) | 2001-07-10 | 2003-01-23 | Elan Pharmaceuticals, Inc. | Aminediols for the treatment of alzheimer's disease |
| WO2003006013A1 (en) | 2001-07-10 | 2003-01-23 | Elan Pharmaceuticals, Inc. | Diaminediols for the treatment of alzheimer's disease |
| US7186539B1 (en) | 2001-08-31 | 2007-03-06 | Pharmacia & Upjohn Company | Method for refolding enzymes |
| CA2462851A1 (en) | 2001-10-04 | 2003-04-10 | Elan Pharmaceuticals, Inc. | Hydroxypropylamines |
| AR039555A1 (es) | 2001-11-08 | 2005-02-23 | Upjohn Co | Derivados n,n'-sustituidos de 1,3-diamino-2-hidroxipropano |
| CA2477243A1 (en) | 2002-02-21 | 2003-09-04 | Pharmacia & Upjohn Company | Modified bace |
| WO2004058686A1 (en) | 2002-04-30 | 2004-07-15 | Elan Pharmaceuticals, Inc. | Hydroxypropyl amides for the treatment of alzheimer’s disease |
| US7442537B1 (en) | 2002-05-10 | 2008-10-28 | Elan Pharmaceuticals, Inc. | Crystals of unliganded beta secretase and/or beta secretase-like proteins and the use thereof |
| WO2004009797A2 (en) * | 2002-07-23 | 2004-01-29 | Incyte Corporation | Protein modification and maintenance molecules |
| BR0316629A (pt) | 2002-11-27 | 2005-10-11 | Elan Pharm Inc | Uréias e carbamatos substituìdos |
| TW200512195A (en) | 2003-04-21 | 2005-04-01 | Elan Pharm Inc | Benzamide 2-hydroxy-3-diaminoalkanes |
| JP4739192B2 (ja) | 2003-05-02 | 2011-08-03 | イーラン ファーマスーティカルズ、インコーポレイテッド | Ｂａｃｅのグリコシル化変異体 |
| WO2005044977A2 (en) * | 2003-06-25 | 2005-05-19 | Diadexus, Inc. | Compositions, splice variants and methods relating to lung specific genes and proteins |
| JP2007528400A (ja) | 2004-03-09 | 2007-10-11 | エラン ファーマシューティカルズ，インコーポレイテッド | 置換ヒドロキシエチルアミン系のアスパラギン酸プロテアーゼ阻害薬 |
| WO2005095454A1 (en) * | 2004-03-25 | 2005-10-13 | Diadexus, Inc. | Lng105 antibody composition and methods of use, and use of lng105 to assess lung cancer risk |
| JP2008505930A (ja) | 2004-07-09 | 2008-02-28 | エラン ファーマシューティカルズ，インコーポレイテッド | オキシム誘導体置換ヒドロキシエチルアミン系のアスパラギン酸プロテアーゼ阻害薬 |
| WO2007047305A1 (en) | 2005-10-12 | 2007-04-26 | Elan Pharmaceuticals, Inc. | Methods of treating amyloidosis using cyclopropyl derivative aspartyl protease inhibitors |
| CA2687750C (en) | 2007-07-06 | 2016-10-18 | Boehringer Ingelheim International Gmbh | Substituted amino-quinazolinones, medicaments comprising said compound, their use and their method of manufacture |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL107250A (en) * | 1993-10-12 | 2001-08-08 | Yeda Res & Dev | Dna molecules involved in programmed cell death, proteins encoded thereby and methods and compositions using said dna molecules and proteins |
| GB9618966D0 (en) * | 1996-09-11 | 1996-10-23 | Smithkline Beecham Plc | Novel compounds |
| US5776759A (en) * | 1996-09-26 | 1998-07-07 | Incyte Pharmaceuticals, Inc. | Two novel human cathepsin proteins |
-
1997
- 1997-11-20 WO PCT/US1997/021684 patent/WO1998022597A2/en not_active Ceased
- 1997-11-20 DK DK97948546T patent/DK0948630T3/da active
- 1997-11-20 ES ES97948546T patent/ES2308791T3/es not_active Expired - Lifetime
- 1997-11-20 AU AU54592/98A patent/AU734220B2/en not_active Ceased
- 1997-11-20 AT AT97948546T patent/ATE393227T1/de active
- 1997-11-20 PT PT97948546T patent/PT948630E/pt unknown
- 1997-11-20 US US08/974,691 patent/US6225103B1/en not_active Expired - Lifetime
- 1997-11-20 JP JP52398598A patent/JP2001503643A/ja not_active Withdrawn
- 1997-11-20 CA CA002271294A patent/CA2271294A1/en not_active Abandoned
- 1997-11-20 EP EP97948546A patent/EP0948630B1/en not_active Expired - Lifetime
- 1997-11-20 DE DE69738653T patent/DE69738653T2/de not_active Expired - Lifetime
-
2007
- 2007-11-15 JP JP2007297327A patent/JP2008118996A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998022597A3 (en) | 1998-07-09 |
| WO1998022597A2 (en) | 1998-05-28 |
| JP2008118996A (ja) | 2008-05-29 |
| DE69738653D1 (de) | 2008-06-05 |
| ES2308791T3 (es) | 2008-12-01 |
| EP0948630B1 (en) | 2008-04-23 |
| AU734220B2 (en) | 2001-06-07 |
| DK0948630T3 (da) | 2008-08-11 |
| AU5459298A (en) | 1998-06-10 |
| CA2271294A1 (en) | 1998-05-28 |
| US6225103B1 (en) | 2001-05-01 |
| DE69738653T2 (de) | 2009-06-04 |
| PT948630E (pt) | 2008-06-11 |
| ATE393227T1 (de) | 2008-05-15 |
| EP0948630A2 (en) | 1999-10-13 |
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