Abstract: 2-Desmethyl ansamycins having a structure according to formula I, where R1, R2, R3, R4, R5 and R6 are as defined herein, and other 2-desmethyl ansamycins are useful as antiproliferative agents
Type:
Grant
Filed:
June 14, 2004
Date of Patent:
July 10, 2007
Assignee:
Kosan Biosciences, Inc.
Inventors:
Zong-Qiang Tian, Robert McDaniel, David C. Myles, Kedar Gautam Patel, Misty Piagentini, Zhan Wang
Abstract: The invention relates to recombinant polyketide synthase enzymes, polyketide modifying proteins, and other proteins involved in polyketide biosynthesis or function. The invention provides domains of geldanamycin and herbimycin polyketide synthases, polynucleotides that encode such enzymes, and to host cells in which such encoding polynucleotides can be advantageously expressed.
Type:
Grant
Filed:
June 13, 2003
Date of Patent:
March 13, 2007
Assignee:
Kosan Biosciences, Inc.
Inventors:
Richard C. Hutchinson, Ralph C. Reid, Zhihao Hu, Andreas Rascher, Andreas Schirmer, Robert McDaniel
Abstract: This invention relates to compounds of formula (I) and to pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, R5, W, X, Y, and Ar are as defined herein. Compounds of formula (I) are useful in the treatment of diseases or conditions characterized by cellular hyperproliferation. This invention also relates to means for the preparation of compounds of formula (I); formulations containing compounds of formula (I); and methods for the use of said compounds and formulations in the treatment of a disease or condition characterized by cellular hyperproliferation, including cancer.
Type:
Grant
Filed:
May 12, 2004
Date of Patent:
February 13, 2007
Assignee:
Kosan Biosciences, Inc.
Inventors:
Gary Ashley, John R. Carney, Brian Metcalf
Abstract: A transposon-based mutagenesis method for altering DNA in Sorangium and other Myxococcales host cells is provided, along with vectors and transposases for use in the method.
Abstract: Recombinant nucleic acids that encode all or a portion of the epothilone polyketide synthase (PKS) are used to express recombinant PKS genes in host cells for the production of epothilones, epothilone derivatives, and polyketides that are useful as cancer chemotherapeutics, fungicides, and immunosuppressants.
Type:
Grant
Filed:
November 28, 2000
Date of Patent:
October 31, 2006
Assignee:
KOSAN Biosciences, Inc.
Inventors:
Bryan Julien, Leonard Katz, Chaitan Khosla, Li Tang, Rainer Ziermann
Abstract: Recombinant host cells of the suborder Cystobacterineae containing recombinant expression vectors that encode heterologous PKS genes can produce polyketides synthesized by the PKS enzymes encoded on those vectors at high levels.
Type:
Application
Filed:
September 20, 2005
Publication date:
October 5, 2006
Applicant:
Kosan Biosciences, Inc.
Inventors:
Bryan Julien, Leonard Katz, Chaitan Khosla
Abstract: Hybrid and novel polyketide synthases and polyketides are produced by use of a multiple vector system. The combinatorial possibilities offered by placing the various catalytic activities of PKS systems on separate vectors permits the construction of improved libraries of PKS and polyketides. In addition, polyketides can be produced in hosts that ordinarily do not produce polyketides by supplying, along with an expression system for the desired PKS, an expression system for holo ACP synthase.
Type:
Application
Filed:
October 27, 2005
Publication date:
July 6, 2006
Applicant:
Kosan Biosciences, Inc.
Inventors:
Philip Barr, Daniel Santi, Gary Ashley, Rainer Ziermann
Abstract: Recombinant host cells of the suborder Cystobacterineae, genus Stizmatella, containing recombinant expression vectors that encode heterologous epothilone polyketide synthase (PKS) genes and can produce epothilones at high levels are provided.
Type:
Grant
Filed:
July 8, 2002
Date of Patent:
June 27, 2006
Assignee:
Kosan Biosciences, Inc.
Inventors:
Bryan Julien, Leonard Katz, Chaitan Khosla
Abstract: Regions of sequence identity are recurrent in some modular polyketide synthase (PKS) gene clusters. Such sequences are potentially detrimental to the stability of PKS gene clusters and expression plasmids for the genes in the gene cluster. PKS gene and gene cluster stability can be improved, and reproducible polyketide titers can be obtained using those genes and gene clusters when the regions of sequence identity are reduced or eliminated by replacing one or more identical or homologous segments with non-homologous segments that encode the same or a substantially similar amino acid sequence.
Type:
Grant
Filed:
April 18, 2002
Date of Patent:
April 25, 2006
Assignee:
Kosan Biosciences, Inc.
Inventors:
Zhihao Hu, Robert McDaniel, Daniel V. Santi
Abstract: Facile methods for preparing diketide and triketide thioesters are disclosed. The resulting thioesters may be used as intermediates in the synthesis of desired polyketides, and may contain functional groups which ultimately reside in side chains on the resulting polyketide and thus can be used further to manipulate the polyketide so as form derivatives. The polyketides produced may also be tailored by glycosylation, hydroxylation and the like. New polyketides and their derivatives and tailored forms are thereby produced.
Type:
Grant
Filed:
August 8, 2002
Date of Patent:
April 4, 2006
Assignee:
Kosan Biosciences, Inc.
Inventors:
Gary Ashley, Isaac C. Chan-Kai, Mark A. Burlingame
Abstract: Recombinant E. coli host cells that comprise recombinant DNA expression vectors that drive expression of methylmalonyl CoA mutase from Propionibacterium shermanii or Streptomyces cinnamonensis as well as Propionibacterium shermanii epimerase can produce S-methylmalonyl CoA, a required substrate for the production of polyketides by most modular polyketide synthases and is not present in wild-type E. coli host cells.
Type:
Grant
Filed:
October 27, 2000
Date of Patent:
March 14, 2006
Assignee:
Kosan Biosciences, Inc.
Inventors:
Daniel Santi, Larry Peck, Linda Dayem, James Kealey
Abstract: Methods are provided for purification of epothilone D and epothilone D analogs from epothilone producing cells such as, for example, Sorangium cellulosum and Myxococcus xanthus (recombinant). Epothilone can be purified from fermentation broth, for example by using resins, chromatography, and crystallization. Epothilone D can be crystallized from a binary solvent system in which water is the forcing solvent.
Abstract: A polyketide or glycosylated polyketide which has the formula: wherein R* is methyl or ethyl; each of R1-R6 is methyl; X1 is OH or H; and/or X2 is=O, OH or H; X3 is OH or H; X4 is OH or H; a pi bond is present at positions 10-11, 8-9, 4-5 and/or 2-3; and wherein at least one of the following characteristics is present: X1 is H; X2 is OH or H; X3 is H; X4 is H; or a pi bond is present at positions 10-11, 8-9, 4-5 and/or 2-3.
Type:
Grant
Filed:
May 9, 2001
Date of Patent:
January 10, 2006
Assignees:
The LeLand Stanford Junior University, Kosan Biosciences, Inc.
Inventors:
Chaitan Khosla, Gary Ashley, Camilla Kao, Robert McDaniel
Abstract: Compounds according to formula I wherein m is 0 or 1; X is and R1, R2, R3 R4, and R5 are as defined herein, are useful as anti-infective agents.
Type:
Application
Filed:
June 30, 2004
Publication date:
December 8, 2005
Applicant:
Kosan Biosciences, Inc.
Inventors:
Yong Li, Yandong Li, Yan Zhu, Chaitan Khosla, David Myles
Abstract: A pharmaceutical solution formulation containing 17-AAG in an amount of up to 15 mg/mL dissolved in a vehicle comprising (i) a first component that is ethanol, in an amount of between about 40 and about 60 volume %; (ii) a second component that is a polyethoxylated castor oil, in an amount of between about 15 to about 50 volume %; and (iii) a third component that is selected from the group consisting of propylene glycol, PEG 300, PEG 400, glycerol, and combinations thereof, in an amount of between about 0 and about 35 volume %.
Abstract: The invention provides strategies, methods, vectors, reagents, and systems for production of synthetic genes, production of libraries of such genes, and manipulation and characterization of the genes and corresponding encoded polypeptides. In one aspect, the synthetic genes can encode polyketide synthase polypeptides and facilitate production of therapeutically or commercially important polyketide compounds.
Type:
Application
Filed:
April 7, 2004
Publication date:
October 13, 2005
Applicant:
Kosan Biosciences, Inc.
Inventors:
Daniel Santi, Sarah Kodumal, Ralph Reid, Kedar Patel
Abstract: Motilide compounds having the formula (I), wherein R1, R2, R3, and R4 are as defined herein, and methods for their preparation and use in the treatment of diseases or conditions characterized by impaired gastric motility.
Type:
Grant
Filed:
August 26, 2003
Date of Patent:
September 20, 2005
Assignee:
Kosan Biosciences, Inc.
Inventors:
Daniel V. Santi, Brian Metcalf, Christopher Carreras, Yaoquan Liu, Robert McDaniel, Eduardo J. Rodriguez
Abstract: Diseases of cellular proliferation can be treated with a combination of leptomycin B and a chemotherapeutic co-agent, for instance an anti-mitotic agent, a DNA cleaver, an alkylating agent, a DNA crosslinking agent, a DNA intercalator, an HSP90 inhibitor, a topoisomerase I inhibitor, a topoisomerase II inhibitor, an immunosuppressant, an anti-metabolite, a COX-2 inhibitor, a nucleoside (purine or pyrimidine) analog, a Ras inhibitor, a farnesyl transferase inhibitor, or a histone deacetylase inhibitor.