WO2000031247A3 - Recombinant methods and materials for producing epothilone and epothilone derivatives - Google Patents

Recombinant methods and materials for producing epothilone and epothilone derivatives Download PDF

Info

Publication number
WO2000031247A3
WO2000031247A3 PCT/US1999/027438 US9927438W WO0031247A3 WO 2000031247 A3 WO2000031247 A3 WO 2000031247A3 US 9927438 W US9927438 W US 9927438W WO 0031247 A3 WO0031247 A3 WO 0031247A3
Authority
WO
WIPO (PCT)
Prior art keywords
epothilone
materials
derivatives
recombinant methods
producing
Prior art date
Application number
PCT/US1999/027438
Other languages
French (fr)
Other versions
WO2000031247A2 (en
Inventor
Bryan Julien
Leonard Katz
Chaitan Khosla
Li Tang
Rainer Ziermann
Original Assignee
Kosan Biosciences Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to EP99960500A priority Critical patent/EP1135470A2/en
Application filed by Kosan Biosciences Inc filed Critical Kosan Biosciences Inc
Priority to IL14306999A priority patent/IL143069A0/en
Priority to CA002350189A priority patent/CA2350189A1/en
Priority to NZ511722A priority patent/NZ511722A/en
Priority to CNB998156787A priority patent/CN100381566C/en
Priority to JP2000584057A priority patent/JP4662635B2/en
Priority to AU17377/00A priority patent/AU768220B2/en
Priority to US09/560,367 priority patent/US6410301B1/en
Publication of WO2000031247A2 publication Critical patent/WO2000031247A2/en
Publication of WO2000031247A3 publication Critical patent/WO2000031247A3/en
Priority to IL143069A priority patent/IL143069A/en
Priority to US10/191,694 priority patent/US7067286B2/en
Priority to US11/231,735 priority patent/US20060223151A1/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D493/00Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D493/00Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08Bridged systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/08Bridged systems
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034Isolating an individual clone by screening libraries
    • C12N15/1058Directional evolution of libraries, e.g. evolution of libraries is achieved by mutagenesis and screening or selection of mixed population of organisms
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/52Genes encoding for enzymes or proenzymes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C12P17/181Heterocyclic compounds containing oxygen atoms as the only ring heteroatoms in the condensed system, e.g. Salinomycin, Septamycin

Abstract

Recombinant nucleic acids that encode all or a portion of the epothilone polyketide synthase (PKS) of sorangium cellulosum are used to express recombinant PKS genes in host cells for the production of epithilones, epothilone derivatives, and polyketides that are useful as cancer chemotherapeutics, fungicides, and immunosuppressants.
PCT/US1999/027438 1998-11-20 1999-11-19 Recombinant methods and materials for producing epothilone and epothilone derivatives WO2000031247A2 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
JP2000584057A JP4662635B2 (en) 1998-11-20 1999-11-19 Recombinant methods and materials for producing epothilone and epothilone derivatives
IL14306999A IL143069A0 (en) 1998-11-20 1999-11-19 Recombinant methods and materials for producing epothilone and epothilone derivatives
CA002350189A CA2350189A1 (en) 1998-11-20 1999-11-19 Recombinant methods and materials for producing epothilone and epothilone derivatives
NZ511722A NZ511722A (en) 1998-11-20 1999-11-19 Recombinant methods and materials for producing epothilone and epothilone derivatives
CNB998156787A CN100381566C (en) 1998-11-20 1999-11-19 Recombinant methods and materials for producing epothilone and eopthilone derivatives
EP99960500A EP1135470A2 (en) 1998-11-20 1999-11-19 Recombinant methods and materials for producing epothilone and epothilone derivatives
AU17377/00A AU768220B2 (en) 1998-11-20 1999-11-19 Recombinant methods and materials for producing epothilone and epothilone derivatives
US09/560,367 US6410301B1 (en) 1998-11-20 2000-04-28 Myxococcus host cells for the production of epothilones
IL143069A IL143069A (en) 1998-11-20 2001-05-10 Recombinant methods and materials for producing epothilone and epothilone derivatives
US10/191,694 US7067286B2 (en) 1998-11-20 2002-07-08 Cystobacterineae host cells containing heterologous PKS genes for the synthesis of polykedtides
US11/231,735 US20060223151A1 (en) 1998-11-20 2005-09-20 Production of polyketides

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US10940198P 1998-11-20 1998-11-20
US60/109,401 1998-11-20
US11938699P 1999-02-10 1999-02-10
US60/119,386 1999-02-10
US12262099P 1999-03-03 1999-03-03
US60/122,620 1999-03-03
US13056099P 1999-04-22 1999-04-22
US60/130,560 1999-04-22

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/443,501 Continuation-In-Part US6303342B1 (en) 1998-11-20 1999-11-19 Recombinant methods and materials for producing epothilones C and D

Publications (2)

Publication Number Publication Date
WO2000031247A2 WO2000031247A2 (en) 2000-06-02
WO2000031247A3 true WO2000031247A3 (en) 2000-12-07

Family

ID=27493695

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/027438 WO2000031247A2 (en) 1998-11-20 1999-11-19 Recombinant methods and materials for producing epothilone and epothilone derivatives

Country Status (10)

Country Link
US (7) US6303342B1 (en)
EP (1) EP1135470A2 (en)
JP (2) JP4662635B2 (en)
KR (3) KR100851418B1 (en)
CN (1) CN100381566C (en)
AU (1) AU768220B2 (en)
CA (1) CA2350189A1 (en)
IL (2) IL143069A0 (en)
NZ (1) NZ511722A (en)
WO (1) WO2000031247A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE41990E1 (en) 1996-12-03 2010-12-07 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof

Families Citing this family (159)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4274583B2 (en) 1996-11-18 2009-06-10 ゲゼルシャフト・フュア・ビオテクノロギッシェ・フォルシュンク・ミット・ベシュレンクテル・ハフツング(ゲー・ベー・エフ) Epothilone C, D, E and F, manufacturing and drugs
US6204388B1 (en) 1996-12-03 2001-03-20 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
US20050043376A1 (en) * 1996-12-03 2005-02-24 Danishefsky Samuel J. Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6399789B1 (en) 1996-12-18 2002-06-04 Kosan Biosciences, Inc. Multi-plasmid method for preparing large libraries of polyketides and non-ribosomal peptides
US6605599B1 (en) 1997-07-08 2003-08-12 Bristol-Myers Squibb Company Epothilone derivatives
US6365749B1 (en) 1997-12-04 2002-04-02 Bristol-Myers Squibb Company Process for the preparation of ring-opened epothilone intermediates which are useful for the preparation of epothilone analogs
FR2775187B1 (en) 1998-02-25 2003-02-21 Novartis Ag USE OF EPOTHILONE B FOR THE MANUFACTURE OF AN ANTIPROLIFERATIVE PHARMACEUTICAL PREPARATION AND A COMPOSITION COMPRISING EPOTHILONE B AS AN IN VIVO ANTIPROLIFERATIVE AGENT
US6380395B1 (en) 1998-04-21 2002-04-30 Bristol-Myers Squibb Company 12, 13-cyclopropane epothilone derivatives
US6498257B1 (en) 1998-04-21 2002-12-24 Bristol-Myers Squibb Company 2,3-olefinic epothilone derivatives
DE19826988A1 (en) * 1998-06-18 1999-12-23 Biotechnolog Forschung Gmbh Epothilone minor components
US6121029A (en) * 1998-06-18 2000-09-19 Novartis Ag Genes for the biosynthesis of epothilones
DE19846493A1 (en) * 1998-10-09 2000-04-13 Biotechnolog Forschung Gmbh DNA sequence coding for products involved in the biosynthesis of polyketide or heteropolyketide compounds, especially epothilone
CN100381566C (en) 1998-11-20 2008-04-16 科森生物科学公司 Recombinant methods and materials for producing epothilone and eopthilone derivatives
US6410301B1 (en) 1998-11-20 2002-06-25 Kosan Biosciences, Inc. Myxococcus host cells for the production of epothilones
AU754459B2 (en) * 1998-12-23 2002-11-14 Bristol-Myers Squibb Company Microbial transformation method for the preparation of an epothilone
US6596875B2 (en) * 2000-02-07 2003-07-22 James David White Method for synthesizing epothilones and epothilone analogs
ATE331028T1 (en) * 1999-04-16 2006-07-15 Kosan Biosciences Inc MULTI-PLASMID PROCESS FOR PRODUCING LARGE LIBRARIES OF POLYKETIDES AND NON-RIBOSOMAL PEPTIDES
WO2001031049A2 (en) * 1999-10-25 2001-05-03 Kosan Biosciences, Inc. Production of polyketides
MXPA02004153A (en) * 1999-10-27 2002-10-17 Kosan Biosciences Inc Heterologous production of polyketides.
US6518421B1 (en) 2000-03-20 2003-02-11 Bristol-Myers Squibb Company Process for the preparation of epothilone analogs
ES2254493T3 (en) * 2000-04-28 2006-06-16 Kosan Biosciences, Inc. HETEROLOGICAL PRODUCTION OF POLICETIDES.
US6998256B2 (en) * 2000-04-28 2006-02-14 Kosan Biosciences, Inc. Methods of obtaining epothilone D using crystallization and /or by the culture of cells in the presence of methyl oleate
US8618085B2 (en) * 2000-04-28 2013-12-31 Koasn Biosciences Incorporated Therapeutic formulations of desoxyepothilones
US6589968B2 (en) 2001-02-13 2003-07-08 Kosan Biosciences, Inc. Epothilone compounds and methods for making and using the same
US20020052028A1 (en) * 2000-08-09 2002-05-02 Daniel Santi Bio-intermediates for use in the chemical synthesis of polyketides
WO2001092991A2 (en) 2000-05-30 2001-12-06 Kosan Biosciences, Inc. Design of polyketide synthase genes
JP2004516011A (en) * 2000-07-25 2004-06-03 コーサン バイオサイエンシーズ, インコーポレイテッド Fermentation process for epothilone
WO2002032916A2 (en) * 2000-09-25 2002-04-25 Kosan Biosciences, Inc. Sixteen-membered macrolide compounds
US7257562B2 (en) 2000-10-13 2007-08-14 Thallion Pharmaceuticals Inc. High throughput method for discovery of gene clusters
US20030077759A1 (en) * 2000-12-28 2003-04-24 Zhihao Hu Plasmids for polyketide production
YU58203A (en) 2001-01-25 2006-08-17 Bristol-Myers Squibb Company Methods of administering epothilone analogs for the treatment of cancer
NZ526871A (en) * 2001-01-25 2006-01-27 Bristol Myers Squibb Co Pharmaceutical dosage forms of epothilones for oral administration
CA2434566A1 (en) 2001-01-25 2002-08-15 Timothy M. Malloy Parenteral formulation containing epothilone analogs
US6893859B2 (en) * 2001-02-13 2005-05-17 Kosan Biosciences, Inc. Epothilone derivatives and methods for making and using the same
HUP0303175A2 (en) 2001-02-20 2003-12-29 Bristol-Myers Squibb Co. Use of epothlone derivatives for preparation of pharmaceutical composition suitable for treatment of refractory tumors
IL157128A0 (en) 2001-02-20 2004-02-08 Bristol Myers Squibb Co Pharmaceutical compositions containing epothilone derivatives
EP1383490B1 (en) 2001-03-14 2012-04-25 Bristol-Myers Squibb Company Combination of an epothilone analog and chemotherapeutic agents for the treatment of proliferative diseases
US20070203346A1 (en) * 2001-04-30 2007-08-30 Oregon State University Method for synthesizing epothilones and epothilone analogs
US6906188B2 (en) * 2001-04-30 2005-06-14 State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Oregon State University Method for synthesizing epothilones and epothilone analogs
US6800653B2 (en) 2001-06-01 2004-10-05 Bristol-Myers Squibb Compnay Epothilone derivatives
TWI315982B (en) 2001-07-19 2009-10-21 Novartis Ag Combinations comprising epothilones and pharmaceutical uses thereof
WO2003014311A2 (en) * 2001-08-06 2003-02-20 Kosan Biosciences, Inc. Methods for altering polyketide synthase genes
WO2003042217A2 (en) * 2001-11-15 2003-05-22 Kosan Biosciences, Inc. Method for making epothilone compounds by bioconversion with microorganisms
US7189549B2 (en) * 2002-06-14 2007-03-13 Kosan Biosciences, Inc. Recombinant polynucleotides encoding pro-geldanamycin producing polyketide synthase and accessory proteins, and uses thereof
US20060089327A1 (en) 2002-01-14 2006-04-27 Hohneker John A Combinations comprising epothilones and anti-metabolites
CN1639319B (en) * 2002-02-25 2010-04-28 高山生物科学股份有限公司 Secondary metabolite congener distribution modulation
AU2003218107A1 (en) 2002-03-12 2003-09-29 Bristol-Myers Squibb Company C12-cyano epothilone derivatives
ES2337134T3 (en) 2002-03-12 2010-04-21 Bristol-Myers Squibb Company DERIVATIVES OF C3-CIANO-EPOTILONE.
TW200403994A (en) 2002-04-04 2004-03-16 Bristol Myers Squibb Co Oral administration of EPOTHILONES
TW200400191A (en) 2002-05-15 2004-01-01 Bristol Myers Squibb Co Pharmaceutical compositions and methods of using C-21 modified epothilone derivatives
EP1575556A2 (en) * 2002-05-20 2005-09-21 Kosan Biosciences, Inc. Methods to administer epothilone d
US7008936B2 (en) 2002-06-14 2006-03-07 Bristol-Myers Squibb Company Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases
US7427493B2 (en) 2002-06-28 2008-09-23 Kosan Biosciences Incorporated Recombinant genes for polyketide modifying enzymes
AU2003256417A1 (en) * 2002-08-13 2004-02-25 Kosan Biosciences, Inc. Transposon-based transformation system
AU2003265608A1 (en) * 2002-08-21 2004-03-11 Kosan Biosciences, Inc. Myxococcus xanthus bacteriophage mx9 transformation and integration system
DE60330407D1 (en) 2002-08-23 2010-01-14 Sloan Kettering Inst Cancer Synthesis of epothilones, intermediates thereof, analogs and their use
US6921769B2 (en) 2002-08-23 2005-07-26 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
US7649006B2 (en) * 2002-08-23 2010-01-19 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
CA2499600C (en) 2002-09-23 2012-08-21 Daniel Benigni Methods for the preparation, isolation and purification of epothilone b, and x-ray crystal structures of epothilone b
CN101177425B (en) * 2003-01-28 2012-07-18 北京华昊中天生物技术有限公司 Novel epothilones compound as well as preparation method and use thereof
US20050171167A1 (en) * 2003-11-04 2005-08-04 Haby Thomas A. Process and formulation containing epothilones and analogs thereof
US20050215604A1 (en) * 2004-03-26 2005-09-29 Kosan Biosciences, Inc. Combination therapies with epothilones and carboplatin
PE20110102A1 (en) 2004-04-07 2011-02-07 Novartis Ag DERIVATIVES OF N- (2-OXO-2-PYRROLIDINYL-1-IL) ETHYL-2-AMINO-ACETAMIDE AS INHIBITORS OF APOPTOSIS PROTEINS (IAP)
US7595187B2 (en) * 2004-11-12 2009-09-29 Wyeth Elaiophylin biosynthetic gene cluster
US20060211736A1 (en) * 2005-01-13 2006-09-21 Wisconsin Alumni Research Foundation Glutarimide-containing polyketide analogs and methods thereof
EP2634252B1 (en) 2005-02-11 2018-12-19 University of Southern California Method of expressing proteins with disulfide bridges
KR100681811B1 (en) * 2005-03-15 2007-02-12 성균관대학교산학협력단 Method for Preparing a Useful Secondary Metabolite by Effective Elimination of Biological By-Products
EP1883627B1 (en) 2005-05-18 2018-04-18 Pharmascience Inc. Bir domain binding compounds
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
WO2007038459A2 (en) 2005-09-27 2007-04-05 Novartis Ag Carboxyamine compounds and their use in the treatment of hdac dependent diseases
EP2022498A3 (en) 2005-11-21 2012-08-15 Novartis AG Neuroendocrine tumour treatment
GB0605120D0 (en) 2006-03-14 2006-04-26 Novartis Ag Organic Compounds
MX2008012728A (en) 2006-04-05 2008-10-14 Novartis Ag Combinations comprising bcr-abl/c-kit/pdgf-r tk inhibitors for treating cancer.
CN101415409B (en) 2006-04-05 2012-12-05 诺瓦提斯公司 Combinations of therapeutic agents for treating cancer
US8008256B2 (en) * 2006-05-01 2011-08-30 University Of Southern California Combination therapy for treatment of cancer
US20090317489A1 (en) 2006-05-09 2009-12-24 Hanspeter Nick Combination Comprising an Iron Chelator and an Anti-Neoplastic Agent and Use Thereof
NZ572836A (en) 2006-05-16 2011-12-22 Pharmascience Inc Iap bir domain binding compounds
EP2081933B1 (en) 2006-09-29 2011-03-23 Novartis AG Pyrazolopyrimidines as pi3k lipid kinase inhibitors
JP2010519209A (en) 2007-02-15 2010-06-03 ノバルティス アーゲー Combination of LBH589 and other therapeutic agents for treating cancer
US9115359B2 (en) * 2007-04-02 2015-08-25 Newsouth Innovations Pty Limited Methods for producing secondary metabolites
KR100901164B1 (en) * 2007-07-16 2009-06-04 성균관대학교산학협력단 Epothilone Producing Strain Transformed with Heterologous Propionyl-CoA Synthetase Gene and Method for Preparing Epothilone Using the Same
WO2009118292A1 (en) 2008-03-24 2009-10-01 Novartis Ag Arylsulfonamide-based matrix metalloprotease inhibitors
MX2010010502A (en) 2008-03-26 2010-10-26 Novartis Ag Hydroxamate-based inhibitors of deacetylases b.
JP2011516045A (en) 2008-03-28 2011-05-26 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Production of dicarboxylic acids using polyketide synthase
WO2009132253A1 (en) 2008-04-24 2009-10-29 Bristol-Myers Squibb Company Use of epothelone d in treating tau-associated diseases including alzheimer's disease
EP2268828A4 (en) * 2008-04-29 2012-08-01 Univ California Producing biofuels using polyketide synthases
US8802394B2 (en) 2008-11-13 2014-08-12 Radu O. Minea Method of expressing proteins with disulfide bridges with enhanced yields and activity
WO2010083617A1 (en) 2009-01-21 2010-07-29 Oncalis Ag Pyrazolopyrimidines as protein kinase inhibitors
EP2391366B1 (en) 2009-01-29 2012-11-28 Novartis AG Substituted benzimidazoles for the treatment of astrocytomas
DK2445903T3 (en) 2009-06-26 2014-06-23 Novartis Ag 1,3-Disubstituted imidazolidin-2-one derivatives as CYP17 inhibitors
US8389526B2 (en) 2009-08-07 2013-03-05 Novartis Ag 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives
WO2011018454A1 (en) 2009-08-12 2011-02-17 Novartis Ag Heterocyclic hydrazone compounds and their uses to treat cancer and inflammation
AU2010284972A1 (en) 2009-08-20 2012-03-08 Novartis Ag Heterocyclic oxime compounds
KR20120050492A (en) 2009-08-26 2012-05-18 노파르티스 아게 Tetra-substituted heteroaryl compounds and their use as mdm2 and/or mdm4 modulators
PE20121471A1 (en) 2009-11-04 2012-11-01 Novartis Ag HELPFUL HETEROCYCLIC SULFONAMIDE DERIVATIVES AS MEK INHIBITORS
CA2780935C (en) 2009-11-13 2022-05-24 U3 Pharma Gmbh Material and methods for treating or preventing her-3 associated diseases
JP5456908B2 (en) 2009-12-08 2014-04-02 ノバルティス アーゲー Heterocyclic sulfonamide derivatives
CU24130B1 (en) 2009-12-22 2015-09-29 Novartis Ag ISOQUINOLINONES AND REPLACED QUINAZOLINONES
US8440693B2 (en) 2009-12-22 2013-05-14 Novartis Ag Substituted isoquinolinones and quinazolinones
EP2534170B1 (en) 2010-02-12 2017-04-19 Pharmascience Inc. Iap bir domain binding compounds
EP2571525A4 (en) 2010-05-18 2016-04-27 Cerulean Pharma Inc Compositions and methods for treatment of autoimmune and other diseases
UA112517C2 (en) 2010-07-06 2016-09-26 Новартіс Аг TETRAHYDROPYRIDOPYRIMIDINE DERIVATIVES
CA2815154A1 (en) 2010-08-06 2012-02-09 U3 Pharma Gmbh Use of her3 binding agents in prostate treatment
JP2013537210A (en) 2010-09-16 2013-09-30 ノバルティス アーゲー 17α-hydroxylase / C17,20-lyase inhibitor
US8852902B2 (en) 2010-11-22 2014-10-07 The Regents Of The University Of California Producing a trimethylpentanoic acid using hybrid polyketide synthases
KR20140012072A (en) 2011-01-28 2014-01-29 아미리스 인코퍼레이티드 Gel-encapsulated microcolony screening
JP2014505088A (en) 2011-02-10 2014-02-27 ノバルティス アーゲー [1,2,4] Triazolo [4,3-b] pyridazine compounds as C-MET tyrosine kinase inhibitors
JP6002210B2 (en) 2011-04-28 2016-10-05 ノバルティス アーゲー 17α-hydroxylase / C17,20-lyase inhibitor
CN103518136A (en) 2011-05-13 2014-01-15 阿迈瑞斯公司 Methods and compositions for detecting microbial production of water-immiscible compounds
EP2718276A1 (en) 2011-06-09 2014-04-16 Novartis AG Heterocyclic sulfonamide derivatives
US8859586B2 (en) 2011-06-20 2014-10-14 Novartis Ag Cyclohexyl isoquinolinone compounds
EP2721008B1 (en) 2011-06-20 2015-04-29 Novartis AG Hydroxy substituted isoquinolinone derivatives as p53 (mdm2 or mdm4) inhibitors
KR20140025530A (en) 2011-06-27 2014-03-04 노파르티스 아게 Solid forms and salts of tetrahydro-pyrido-pyrimidine derivatives
ES2691650T3 (en) 2011-09-15 2018-11-28 Novartis Ag 3- (quinolin-6-yl-thio) - [1,2,4] -triazolo- [4,3-a] -pyridines 6-substituted as inhibitors of tyrosine kinase c-Met
US8969341B2 (en) 2011-11-29 2015-03-03 Novartis Ag Pyrazolopyrrolidine compounds
AP4055A (en) 2011-12-22 2017-03-07 Novartis Ag Dihydro-benzo-oxazine and dihydro-pyrido-oxazine derivatives
EP2794594A1 (en) 2011-12-22 2014-10-29 Novartis AG Quinoline derivatives
CA2859867A1 (en) 2011-12-23 2013-06-27 Novartis Ag Compounds for inhibiting the interaction of bcl2 with binding partners
KR20140107573A (en) 2011-12-23 2014-09-04 노파르티스 아게 Compounds for inhibiting the interaction of bcl2 with binding partners
MX2014007725A (en) 2011-12-23 2015-01-12 Novartis Ag Compounds for inhibiting the interaction of bcl2 with binding partners.
KR20140107574A (en) 2011-12-23 2014-09-04 노파르티스 아게 Compounds for inhibiting the interaction of bcl2 with binding partners
CA2859869A1 (en) 2011-12-23 2013-06-27 Novartis Ag Compounds for inhibiting the interaction of bcl2 with binding partners
US8815926B2 (en) 2012-01-26 2014-08-26 Novartis Ag Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases
PT2861579T (en) 2012-05-15 2018-04-27 Novartis Ag Benzamide derivatives for inhibiting the activity of abl1, abl2 and bcr-abl1
US9278981B2 (en) 2012-05-15 2016-03-08 Novartis Ag Compounds and compositions for inhibiting the activity of ABL1, ABL2 and BCR-ABL1
EA201492007A1 (en) 2012-05-15 2015-03-31 Новартис Аг DERIVATIVES OF BENZAMIDE FOR INHIBITION OF ABL1, ABL2 AND BCR-ABL1 ACTIVITY
JP6080947B2 (en) 2012-05-15 2017-02-15 ノバルティス アーゲー Compounds and compositions for inhibiting the activity of ABL1, ABL2 and BCR-ABL1
EP2855483B1 (en) 2012-05-24 2017-10-25 Novartis AG Pyrrolopyrrolidinone compounds
BR112014031421A2 (en) 2012-06-15 2017-06-27 Brigham & Womens Hospital Inc cancer treatment compositions and methods for producing them
US10090498B2 (en) 2012-06-24 2018-10-02 SeeScan, Inc. Modular battery pack apparatus, systems, and methods including viral data and/or code transfer
CA2879178C (en) 2012-08-07 2020-11-24 Amyris, Inc. Methods for stabilizing production of acetyl-coenzyme a derived compounds
SG11201502452RA (en) 2012-10-02 2015-05-28 Epitherapeutics Aps Inhibitors of histone demethylases
TW201422625A (en) 2012-11-26 2014-06-16 Novartis Ag Solid form of dihydro-pyrido-oxazine derivative
US9556180B2 (en) 2013-01-22 2017-01-31 Novartis Ag Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the P53/MDM2 interaction
EP2948451B1 (en) 2013-01-22 2017-07-12 Novartis AG Substituted purinone compounds
WO2014128612A1 (en) 2013-02-20 2014-08-28 Novartis Ag Quinazolin-4-one derivatives
EA030451B1 (en) 2013-02-27 2018-08-31 Эпитерапьютикс Апс Inhibitors of histone demethylases
CA2903053C (en) 2013-03-15 2023-01-17 Amyris, Inc. Use of phosphoketolase and phosphotransacetylase for production of acetyl-coenzyme a derived compounds
US20150018376A1 (en) 2013-05-17 2015-01-15 Novartis Ag Pyrimidin-4-yl)oxy)-1h-indole-1-carboxamide derivatives and use thereof
UY35675A (en) 2013-07-24 2015-02-27 Novartis Ag SUBSTITUTED DERIVATIVES OF QUINAZOLIN-4-ONA
EP3663392A1 (en) 2013-08-07 2020-06-10 Amyris, Inc. Methods for stabilizing production of acetyl-coenzyme a derived compounds
WO2015022663A1 (en) 2013-08-14 2015-02-19 Novartis Ag Compounds and compositions as inhibitors of mek
US9227969B2 (en) 2013-08-14 2016-01-05 Novartis Ag Compounds and compositions as inhibitors of MEK
WO2015022664A1 (en) 2013-08-14 2015-02-19 Novartis Ag Compounds and compositions as inhibitors of mek
EP3046921A4 (en) 2013-09-22 2017-02-22 Calitor Sciences, LLC Substituted aminopyrimidine compounds and methods of use
US10233431B2 (en) 2014-02-26 2019-03-19 The Regents Of The University Of California Producing 3-hydroxycarboxylic acid and ketone using polyketide synthases
WO2015148869A1 (en) 2014-03-28 2015-10-01 Calitor Sciences, Llc Substituted heteroaryl compounds and methods of use
CA2943824A1 (en) 2014-03-31 2015-10-08 Gilead Sciences, Inc. Inhibitors of histone demethylases
US10426753B2 (en) 2014-04-03 2019-10-01 Invictus Oncology Pvt. Ltd. Supramolecular combinatorial therapeutics
KR101601424B1 (en) * 2014-06-02 2016-03-09 이화여자대학교 산학협력단 Expression vector and its use
KR101606635B1 (en) * 2014-06-02 2016-03-28 이화여자대학교 산학협력단 Expression cassettes and their use
AU2015306662A1 (en) 2014-08-27 2017-03-09 Gilead Sciences, Inc. Compounds and methods for inhibiting histone demethylases
US10988513B2 (en) 2015-06-25 2021-04-27 Amyris, Inc. Maltose dependent degrons, maltose-responsive promoters, stabilization constructs, and their use in production of non-catabolic compounds
JP2018527362A (en) 2015-09-11 2018-09-20 サンシャイン・レイク・ファーマ・カンパニー・リミテッドSunshine Lake Pharma Co.,Ltd. Substituted heteroaryl compounds and methods of use
US10683297B2 (en) 2017-11-19 2020-06-16 Calitor Sciences, Llc Substituted heteroaryl compounds and methods of use
WO2019143874A1 (en) 2018-01-20 2019-07-25 Sunshine Lake Pharma Co., Ltd. Substituted aminopyrimidine compounds and methods of use
CN108658949B (en) * 2018-06-29 2021-05-25 云南大学 Compound used as antitumor drug and production method thereof
FR3087650B1 (en) 2018-10-31 2021-01-29 Bio Even FLAVINE ADENINE DINUCLEOTIDE (FAD) FOR USE FOR THE PREVENTION AND / OR TREATMENT OF CANCER
CN113969255A (en) * 2020-07-24 2022-01-25 北京华昊中天生物医药股份有限公司 Recombinant bacterium for producing de-epoxidized epothilone B and application thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998022461A1 (en) * 1996-11-18 1998-05-28 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilone c, d, e and f, production process, and their use as cytostatic as well as phytosanitary agents
WO1999066028A2 (en) * 1998-06-18 1999-12-23 Novartis Ag Genes for the biosynthesis of epothilones
WO2000022139A2 (en) * 1998-10-09 2000-04-20 Bristol-Myers Squibb Company Dna sequences for enzymatic synthesis of polyketide or heteropolyketide compounds

Family Cites Families (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8608080D0 (en) 1986-04-02 1986-05-08 Fujisawa Pharmaceutical Co Solid dispersion composition
US5252474A (en) 1989-03-31 1993-10-12 Merck & Co., Inc. Cloning genes from Streptomyces avermitilis for avermectin biosynthesis and the methods for their use
KR0159766B1 (en) 1989-10-16 1998-12-01 후지사와 토모키치로 Hair revitalizing agent
GB8925797D0 (en) 1989-11-15 1990-01-04 Fisons Plc Compositions
WO1993013663A1 (en) 1992-01-17 1993-07-22 Abbott Laboratories Method of directing biosynthesis of specific polyketides
US5824513A (en) 1991-01-17 1998-10-20 Abbott Laboratories Recombinant DNA method for producing erythromycin analogs
PT501921E (en) 1991-03-01 2001-12-28 Syngenta Participations Ag PROCESS FOR THE GENETIC MANIPULATION OF MIXOBACTERIAS
DE4138042C2 (en) 1991-11-19 1993-10-14 Biotechnolog Forschung Gmbh Epothilones, their production processes and agents containing these compounds
US5264355A (en) 1992-07-02 1993-11-23 Merck & Co., Inc. Methlating enzyme from streptomyces MA6858
US5672491A (en) 1993-09-20 1997-09-30 The Leland Stanford Junior University Recombinant production of novel polyketides
PT725778E (en) 1993-09-20 2002-03-28 Univ Leland Stanford Junior RECOMBINANT PRODUCTION OF NEW POLYETTIDES
US6066721A (en) 1995-07-06 2000-05-23 Stanford University Method to produce novel polyketides
US5712146A (en) 1993-09-20 1998-01-27 The Leland Stanford Junior University Recombinant combinatorial genetic library for the production of novel polyketides
WO1998049315A2 (en) 1997-04-30 1998-11-05 Kosan Biosciences, Inc. Combinatorial polyketide libraries produced using a modular pks gene cluster as scaffold
US5605793A (en) 1994-02-17 1997-02-25 Affymax Technologies N.V. Methods for in vitro recombination
WO1997002358A1 (en) 1995-07-06 1997-01-23 The Leland Stanford Junior University Cell-free synthesis of polyketides
EP0861321B1 (en) 1995-10-13 2006-05-31 President And Fellows Of Harvard College Phosphopantetheinyl transferases and uses thereof
EP0903348B2 (en) 1995-11-17 2008-08-27 Gesellschaft für Biotechnologische Forschung mbH (GBF) Epothilone derivatives and preparation thereof
US5776735A (en) 1995-12-04 1998-07-07 Pfizer Inc. Process for dienone macrolides
US5998194A (en) 1995-12-21 1999-12-07 Abbott Laboratories Polyketide-associated sugar biosynthesis genes
US5783431A (en) 1996-04-24 1998-07-21 Chromaxome Corporation Methods for generating and screening novel metabolic pathways
US5969145A (en) 1996-08-30 1999-10-19 Novartis Ag Process for the production of epothilones and intermediate products within the process
EP0923583A1 (en) 1996-08-30 1999-06-23 Novartis AG Method for producing epothilones, and intermediate products obtained during the production process
WO1999001124A1 (en) 1996-12-03 1999-01-14 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6441186B1 (en) 1996-12-13 2002-08-27 The Scripps Research Institute Epothilone analogs
US6380394B1 (en) 1996-12-13 2002-04-30 The Scripps Research Institute Epothilone analogs
US6033883A (en) 1996-12-18 2000-03-07 Kosan Biosciences, Inc. Production of polyketides in bacteria and yeast
US6605599B1 (en) 1997-07-08 2003-08-12 Bristol-Myers Squibb Company Epothilone derivatives
NZ501998A (en) 1997-07-10 2001-04-27 Kosan Biosciences Inc Production of polyketides in plants
US7407975B2 (en) 1997-08-09 2008-08-05 Bayer Schering Pharma Ag Epothilone derivatives, method for producing same and their pharmaceutical use
DE19741899A1 (en) 1997-09-22 1999-03-25 Hahl Erwin Gmbh Synthetic bristles for moving brushes for automatic car wash
US6365749B1 (en) 1997-12-04 2002-04-02 Bristol-Myers Squibb Company Process for the preparation of ring-opened epothilone intermediates which are useful for the preparation of epothilone analogs
US6090601A (en) 1998-01-23 2000-07-18 Kosan Bioscience Sorangium polyketide synthase
US6280999B1 (en) * 1998-01-23 2001-08-28 Kosan Bioscience Sorangium polyketide synthases and encoding DNA therefor
AR017979A1 (en) 1998-02-05 2001-10-24 Novartis Ag PHARMACEUTICAL FORMULATIONS OF EPOTILONES, METHOD FOR THE PREPARATION AND USE OF THE SAME FOR THE MANUFACTURE OF A MEDICINAL PRODUCT
DE19804673A1 (en) 1998-02-06 1999-08-12 Studiengesellschaft Kohle Mbh Process for the preparation of macrocyclic products by ring-closing diine metathesis
US6194181B1 (en) 1998-02-19 2001-02-27 Novartis Ag Fermentative preparation process for and crystal forms of cytostatics
FR2775187B1 (en) 1998-02-25 2003-02-21 Novartis Ag USE OF EPOTHILONE B FOR THE MANUFACTURE OF AN ANTIPROLIFERATIVE PHARMACEUTICAL PREPARATION AND A COMPOSITION COMPRISING EPOTHILONE B AS AN IN VIVO ANTIPROLIFERATIVE AGENT
ATE307123T1 (en) 1998-02-25 2005-11-15 Sloan Kettering Inst Cancer SYNTHESIS OF EPOTHILONES, THEIR INTERMEDIATE PRODUCTS AND ANALOGUE COMPOUNDS
US6498257B1 (en) 1998-04-21 2002-12-24 Bristol-Myers Squibb Company 2,3-olefinic epothilone derivatives
US6380395B1 (en) 1998-04-21 2002-04-30 Bristol-Myers Squibb Company 12, 13-cyclopropane epothilone derivatives
DE19826988A1 (en) 1998-06-18 1999-12-23 Biotechnolog Forschung Gmbh Epothilone minor components
US6121029A (en) 1998-06-18 2000-09-19 Novartis Ag Genes for the biosynthesis of epothilones
WO1999067253A2 (en) 1998-06-22 1999-12-29 Novartis Ag Desmethyl epothilones
WO2000000485A1 (en) 1998-06-30 2000-01-06 Schering Aktiengesellschaft Epothilon derivatives, their preparation process, intermediate products and their pharmaceutical use
US6221641B1 (en) 1998-07-02 2001-04-24 Leland Stanford Junior University Method for making polyketides
CN100381566C (en) 1998-11-20 2008-04-16 科森生物科学公司 Recombinant methods and materials for producing epothilone and eopthilone derivatives
US6410301B1 (en) 1998-11-20 2002-06-25 Kosan Biosciences, Inc. Myxococcus host cells for the production of epothilones
ES2254493T3 (en) 2000-04-28 2006-06-16 Kosan Biosciences, Inc. HETEROLOGICAL PRODUCTION OF POLICETIDES.
US6489314B1 (en) 2001-04-03 2002-12-03 Kosan Biosciences, Inc. Epothilone derivatives and methods for making and using the same
US6589968B2 (en) 2001-02-13 2003-07-08 Kosan Biosciences, Inc. Epothilone compounds and methods for making and using the same
US6998256B2 (en) 2000-04-28 2006-02-14 Kosan Biosciences, Inc. Methods of obtaining epothilone D using crystallization and /or by the culture of cells in the presence of methyl oleate
US6893859B2 (en) 2001-02-13 2005-05-17 Kosan Biosciences, Inc. Epothilone derivatives and methods for making and using the same
AU2002338336A1 (en) 2001-04-03 2002-10-21 Kosan Biosciences, Inc. Epothilone derivatives and methods for making and using the same
EP3318214B1 (en) 2017-04-21 2020-04-15 Siemens Healthcare GmbH Medical imaging device with smartglasses and method for supporting a person using a medical imaging device

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998022461A1 (en) * 1996-11-18 1998-05-28 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilone c, d, e and f, production process, and their use as cytostatic as well as phytosanitary agents
WO1999066028A2 (en) * 1998-06-18 1999-12-23 Novartis Ag Genes for the biosynthesis of epothilones
WO2000022139A2 (en) * 1998-10-09 2000-04-20 Bristol-Myers Squibb Company Dna sequences for enzymatic synthesis of polyketide or heteropolyketide compounds

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHOU T. C. ET AL.: "DESOXYEPITHILONE B: AN EFFICACIOUS MICROTUBULE-TARGETED ANTITUMOR AGENT WITH A PROMISING IN VIVO PROFILE RELATIVE TO EPOTHILONE B.", PROC. NATL. ACAD. SCI. USA, vol. 95, no. 16, 4 August 1998 (1998-08-04), pages 9642 - -7, XP000910107 *
MOLNÁR I. ET AL.: "The biosynthetic gene cluster for ... epothilones A and B from Sorangium cellulosum So ce90.", CHEMISTRY & BIOLOGY VOL 7 NO 2, 5 January 2000 (2000-01-05), pages 97 - 109, XP000904734 *
TANG, L. ET AL.: "Cloning and heterologous expression of the epithilone gene cluster.", SCIENCE, vol. 287, 28 January 2000 (2000-01-28), pages 640 - 42, XP000213584 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE41990E1 (en) 1996-12-03 2010-12-07 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof

Also Published As

Publication number Publication date
US20090170172A1 (en) 2009-07-02
EP1135470A2 (en) 2001-09-26
US7402421B2 (en) 2008-07-22
KR100851418B1 (en) 2008-08-08
US7129071B1 (en) 2006-10-31
US6303342B1 (en) 2001-10-16
AU1737700A (en) 2000-06-13
US6583290B1 (en) 2003-06-24
JP2002530107A (en) 2002-09-17
WO2000031247A2 (en) 2000-06-02
US6921650B1 (en) 2005-07-26
JP4662635B2 (en) 2011-03-30
CN1333820A (en) 2002-01-30
KR20060124789A (en) 2006-12-05
JP2007097595A (en) 2007-04-19
IL143069A0 (en) 2002-04-21
KR100716272B1 (en) 2007-05-09
US7732186B2 (en) 2010-06-08
US20040253697A1 (en) 2004-12-16
KR20010093103A (en) 2001-10-27
CA2350189A1 (en) 2000-06-02
CN100381566C (en) 2008-04-16
KR20070087132A (en) 2007-08-27
US6858411B1 (en) 2005-02-22
AU768220B2 (en) 2003-12-04
IL143069A (en) 2008-06-05
NZ511722A (en) 2004-05-28

Similar Documents

Publication Publication Date Title
WO2000031247A3 (en) Recombinant methods and materials for producing epothilone and epothilone derivatives
WO2000026349A3 (en) Recombinant oleandolide polyketide synthase
HK1054967A1 (en) Method of amplifying nucleic acid by using double-stranded nucleic acid as template
WO2004031376A3 (en) Sesquiterpene synthases and methods of use
WO2002026933A3 (en) Isoprenoid production
WO2002018587A1 (en) Process for producing biopterins
WO2003046173A1 (en) siRNA EXPRESSION SYSTEM AND PROCESS FOR PRODUCING FUNCTIONAL GENE-KNOCKDOWN CELLS AND THE LIKE USING THE SAME
AU2001269837A1 (en) Process for producing microfluidic articles
WO2001020035A3 (en) Methods and compositions for linear isothermal amplification of polynucleotide sequences
WO2004047742A3 (en) Multivalent aptamer therapeutics with improved pharmacodynamic properties and methods of making and using the same
WO1999066028A3 (en) Genes for the biosynthesis of epothilones
WO2000032757A3 (en) Plant vitamin e biosynthetic enzymes
WO2005047505A3 (en) Methods and products for expression of micro rnas
WO2003102214A3 (en) Method for efficient rna interference in mammalian cells
AU2001242299A1 (en) Fungal transcriptional activator useful in methods for producing polypeptides
WO2006072078A3 (en) Bioproduction of astaxanthin using mutant carotenoid ketolase and cartonenoid hydroxylase genes
WO2002103046A3 (en) Happier mapping
WO1999061599A3 (en) Recombinant narbonolide polyketide synthase
FR2804971B1 (en) DNA ENCODING ACETOHYDROXYACIDE SYNTHASE, BACTERIA CONTAINING SAME, AND METHOD FOR PRODUCING L-VALINE BY CULTURING THE SAME
WO2003072798A3 (en) Method for generating amplified rna
WO2005052163A3 (en) Sesquiterpene synthases from patchouli
WO2000004166A3 (en) Plant cellulose synthases
WO2001077306A3 (en) Plant raffinose saccharide biosynthetic enzymes
AU2002219140A1 (en) Modulating gene expression in insects by using double-stranded rna (dsrna)
WO2002088370A3 (en) Autogene nucleic acids encoding a secretable rna polymerase

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 99815678.7

Country of ref document: CN

ENP Entry into the national phase

Ref document number: 2000 17377

Country of ref document: AU

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 09560367

Country of ref document: US

AK Designated states

Kind code of ref document: A2

Designated state(s): AL AM AU BA BB BG BR CA CN CR CU CZ DM EE GD GE HR HU IL IS JP KG KP KR LC LK LR LT LV MD MG MK MN MX NO NZ PL RO SG SI SK TR TT UA UZ VN ZA

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AL AM AU BA BB BG BR CA CN CR CU CZ DM EE GD GE HR HU IL IS JP KG KP KR LC LK LR LT LV MD MG MK MN MX NO NZ PL RO SG SI SK TR TT UA UZ VN ZA

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

ENP Entry into the national phase

Ref document number: 2350189

Country of ref document: CA

Ref document number: 2350189

Country of ref document: CA

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 143069

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: 1999960500

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 511722

Country of ref document: NZ

ENP Entry into the national phase

Ref document number: 2000 584057

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: PA/a/2001/005097

Country of ref document: MX

Ref document number: 1020017006398

Country of ref document: KR

Ref document number: 17377/00

Country of ref document: AU

WWP Wipo information: published in national office

Ref document number: 1999960500

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1020017006398

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 10191694

Country of ref document: US

WWG Wipo information: grant in national office

Ref document number: 17377/00

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 11231735

Country of ref document: US

WWG Wipo information: grant in national office

Ref document number: 1020017006398

Country of ref document: KR