KR20000015993A - 가교된 단백질 결정 제제 및 유기 용매 중에서 상기 제제를촉매로서 사용하는 방법 - Google Patents
가교된 단백질 결정 제제 및 유기 용매 중에서 상기 제제를촉매로서 사용하는 방법 Download PDFInfo
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- KR20000015993A KR20000015993A KR1019980709554A KR19980709554A KR20000015993A KR 20000015993 A KR20000015993 A KR 20000015993A KR 1019980709554 A KR1019980709554 A KR 1019980709554A KR 19980709554 A KR19980709554 A KR 19980709554A KR 20000015993 A KR20000015993 A KR 20000015993A
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Classifications
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- 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)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/18—Carboxylic ester hydrolases (3.1.1)
- C12N9/20—Triglyceride splitting, e.g. by means of lipase
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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
- C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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| US8/652,964 | 1996-05-24 | ||
| US08/652,964 US5932212A (en) | 1996-05-24 | 1996-05-24 | Crosslinked protein crystal formulations and their use as catalysts in organic solvents |
Publications (1)
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| KR20000015993A true KR20000015993A (ko) | 2000-03-25 |
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| KR1019980709554A Withdrawn KR20000015993A (ko) | 1996-05-24 | 1997-05-20 | 가교된 단백질 결정 제제 및 유기 용매 중에서 상기 제제를촉매로서 사용하는 방법 |
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| EP (1) | EP0906417B1 (forum.php) |
| JP (2) | JP4279351B2 (forum.php) |
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| DK (1) | DK0906417T3 (forum.php) |
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| WO1992009750A1 (en) * | 1990-11-29 | 1992-06-11 | Willis Richard R | Floating contaminant containment systems |
| US6140475A (en) * | 1997-04-11 | 2000-10-31 | Altus Biologics Inc. | Controlled dissolution crosslinked protein crystals |
| JP4433100B2 (ja) * | 1997-06-20 | 2010-03-17 | ニューヨーク ユニヴァーシティ | チップ及びライブラリの大量製造における物質溶液の静電噴霧 |
| US6833275B1 (en) * | 1997-07-22 | 2004-12-21 | Roche Diagnostics Gmbh | Gold conjugates containing detergent |
| DK1009759T3 (da) * | 1997-09-05 | 2008-08-04 | Altus Pharmaceuticals Inc | Carbohydrat-tværbundne glycoproteinkrystaller |
| US6500933B1 (en) | 1997-09-05 | 2002-12-31 | Altus Biologics Inc. | Methods of preparing carbohydrate crosslinked glycoprotein crystals |
| ZA988461B (en) * | 1997-09-18 | 1999-03-30 | Idec Pharma Corp | Synergistic composition and methods for treating neoplastic or cancerous growths and for restoring or boosting hematopoiesis |
| US6541606B2 (en) * | 1997-12-31 | 2003-04-01 | Altus Biologics Inc. | Stabilized protein crystals formulations containing them and methods of making them |
| SG121739A1 (en) * | 1998-04-27 | 2006-05-26 | Altus Pharmaceuticals Inc | Stabilized protein crystals, formulations containing them and methods of making them |
| IL142393A0 (en) * | 1998-10-09 | 2002-03-10 | Altus Biologics Inc | Non-homogeneous systems for the resolution of enantiomeric mixtures |
| US6979561B1 (en) | 1998-10-09 | 2005-12-27 | Gilead Sciences, Inc. | Non-homogeneous systems for the resolution of enantiomeric mixtures |
| DE19903125B4 (de) * | 1999-01-27 | 2006-01-05 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Trocknung von Kristallen von Insulin oder Insulinanaloga |
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| US20040014195A1 (en) * | 1999-12-29 | 2004-01-22 | Diversa Corporation | Nitrilases, nucleic acids encoding them and methods for making and using them |
| US7521216B2 (en) * | 1999-12-29 | 2009-04-21 | Verenium Corporation | Nitrilases and methods for making and using them |
| US7608445B1 (en) | 1999-12-29 | 2009-10-27 | Verenium Corporation | Nitrilases, nucleic acids encoding them and methods for making and using them |
| US7300775B2 (en) * | 1999-12-29 | 2007-11-27 | Verenium Corporation | Methods for producing α-substituted carboxylic acids using nitrilases and strecker reagents |
| US20010046493A1 (en) * | 2000-02-24 | 2001-11-29 | Alex Margolin | Lipase-containing composition and methods of use thereof |
| WO2001090733A1 (en) * | 2000-05-23 | 2001-11-29 | Radiometer Medical A/S | A sensor membrane, a method for the preparation thereof, a sensor and a layered membrane structure for such sensor |
| WO2002072636A2 (en) | 2000-12-28 | 2002-09-19 | Altus Biologics Inc. | Crystals of whole antibodies and fragments thereof and methods for making and using them |
| CA2451185A1 (en) | 2001-06-21 | 2003-01-03 | Altus Biologics, Inc. | Spherical protein particles and methods of making and using them |
| US7932064B2 (en) | 2002-06-13 | 2011-04-26 | Verenium Corporation | Processes for making (R)-ethyl 4-cyano-3-hydroxybutyric acid |
| US9035123B2 (en) | 2002-10-01 | 2015-05-19 | The Procter & Gamble Company | Absorbent article having a lotioned topsheet |
| ZA200505306B (en) * | 2002-12-31 | 2006-09-27 | Altus Pharmaceuticals Inc | Complexes of protein crystals and ionic polymers |
| SG176314A1 (en) * | 2002-12-31 | 2011-12-29 | Altus Pharmaceuticals Inc | Human growth hormone crystals and methods for preparing them |
| US20090035828A1 (en) * | 2004-01-01 | 2009-02-05 | Tholath Emilia Abraham | Method For the Preparation of Cross Linked Protein Crystals |
| ES2614157T3 (es) * | 2004-10-14 | 2017-05-29 | Eli Lilly And Co. | Composiciones que contienen lipasa, proteasa y amilasa para el tratamiento de la insuficiencia pancreática |
| WO2007050100A2 (en) * | 2004-11-24 | 2007-05-03 | Industrial Science & Technology Network, Inc. | Immobilized enzymes and processes for preparing and using same |
| US20060223765A1 (en) * | 2005-03-30 | 2006-10-05 | Kimberly-Clark Worldwide, Inc. | Method for inhibiting and/or treating vaginal infection |
| GB0513888D0 (en) * | 2005-07-06 | 2005-08-10 | Btg Int Ltd | Core 2 GLCNAC-T Inhibitors II |
| US20100196344A1 (en) * | 2005-10-14 | 2010-08-05 | Cystic Fibrosis Foundation Therapeutics, Inc. | Compositions and methods for treating pancreatic insufficiency |
| CA2634053A1 (en) * | 2005-12-23 | 2007-07-05 | Altus Pharmaceuticals Inc. | Compositions comprising polycation-complexed protein crystals and methods of treatment using them |
| US20100047413A1 (en) * | 2006-09-15 | 2010-02-25 | Cabalka Tourtellotte Leanne M | Method of using amphiphilic multiblock copolymers in food |
| EP2115153B1 (en) | 2007-03-01 | 2013-06-05 | BP Corporation North America Inc. | Nitrilases, nucleic acids encoding them and methods for making and using them |
| IL183084A0 (en) * | 2007-05-09 | 2007-09-20 | Trans Biodisel Ltd | Modified-immobilized enzymes of high tolerance to hydrophilic substrates in organic media |
| CN101717766B (zh) * | 2009-12-01 | 2012-07-18 | 暨南大学 | 蛋白质酶的微水介质固定化方法 |
| AU2011272825A1 (en) | 2010-06-30 | 2013-01-10 | Codexis, Inc. | Chemically modified carbonic anhydrases useful in carbon capture systems |
| US9303255B2 (en) | 2010-08-26 | 2016-04-05 | Aisin Seiki Kabushiki Kaisha | Electrode having enzyme crystals immobilized thereon, method for producing electrode having enzyme crystals immobilized thereon, and biological fuel cell and biosensor provided with electrode having enzyme crystals immobilized thereon |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4267234A (en) * | 1978-03-17 | 1981-05-12 | California Institute Of Technology | Polyglutaraldehyde synthesis and protein bonding substrates |
| US4369226A (en) * | 1979-03-19 | 1983-01-18 | California Institute Of Technology | Polyglutaraldehyde synthesis and protein bonding substrates |
| US5152903A (en) * | 1988-12-19 | 1992-10-06 | American Cyanamid Company | Cross-linked cationic polymeric microparticles |
| ATE240391T1 (de) * | 1990-08-03 | 2003-05-15 | Vertex Pharma | Verwendung von vernetzten kristallen als neuem verfahren zur immobilisierung von enzymen |
| GB9309243D0 (en) * | 1993-05-05 | 1993-06-16 | Allied Colloids Ltd | Enzyme dispersions,their production and compositions containing them |
| EP0698090B1 (en) * | 1993-05-20 | 1997-11-26 | Loders Croklaan B.V. | Process for preparing immobilized lipases |
| ATE193319T1 (de) * | 1993-12-03 | 2000-06-15 | Buckman Labor Inc | Enzymstabilisierung durch blockcopolymere |
| DE4344211A1 (de) * | 1993-12-23 | 1995-06-29 | Basf Ag | Verfahren zur Erhöhung der Aktivität von hydrolytischen Enzymen |
-
1996
- 1996-05-24 US US08/652,964 patent/US5932212A/en not_active Expired - Lifetime
-
1997
- 1997-05-19 ZA ZA9704325A patent/ZA974325B/xx unknown
- 1997-05-20 AT AT97925652T patent/ATE393216T1/de not_active IP Right Cessation
- 1997-05-20 JP JP54264897A patent/JP4279351B2/ja not_active Expired - Fee Related
- 1997-05-20 DE DE69738648T patent/DE69738648T2/de not_active Expired - Lifetime
- 1997-05-20 EP EP97925652A patent/EP0906417B1/en not_active Expired - Lifetime
- 1997-05-20 AU AU30728/97A patent/AU3072897A/en not_active Abandoned
- 1997-05-20 AR ARP970102139A patent/AR007211A1/es unknown
- 1997-05-20 DK DK97925652T patent/DK0906417T3/da active
- 1997-05-20 KR KR1019980709554A patent/KR20000015993A/ko not_active Withdrawn
- 1997-05-20 WO PCT/US1997/008526 patent/WO1997044445A1/en not_active Application Discontinuation
- 1997-05-21 ID IDP971682A patent/ID17817A/id unknown
- 1997-05-21 IN IN913CA1997 patent/IN191060B/en unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| ATE393216T1 (de) | 2008-05-15 |
| DE69738648T2 (de) | 2009-05-28 |
| DK0906417T3 (da) | 2008-07-21 |
| US5932212A (en) | 1999-08-03 |
| AR007211A1 (es) | 1999-10-13 |
| JP2000514282A (ja) | 2000-10-31 |
| JP4279351B2 (ja) | 2009-06-17 |
| IN191060B (forum.php) | 2003-09-13 |
| EP0906417A1 (en) | 1999-04-07 |
| AU3072897A (en) | 1997-12-09 |
| JP2008061652A (ja) | 2008-03-21 |
| US6042824A (en) | 2000-03-28 |
| EP0906417B1 (en) | 2008-04-23 |
| ID17817A (id) | 1998-01-29 |
| WO1997044445A1 (en) | 1997-11-27 |
| DE69738648D1 (de) | 2008-06-05 |
| ZA974325B (en) | 1997-12-18 |
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