Patents by Inventor Frances H. Arnold
Frances H. Arnold has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20140242647Abstract: The present invention provides methods for catalyzing the conversion of an olefin to any compound containing one or more cyclopropane functional groups using heme enzymes. In certain aspects, the present invention provides a method for producing a cyclopropanation product comprising providing an olefinic substrate, a diazo reagent, and a heme enzyme; and admixing the components in a reaction for a time sufficient to produce a cyclopropanation product. In other aspects, the present invention provides heme enzymes including variants and fragments thereof that are capable of carrying out in vivo and in vitro olefin cyclopropanation reactions. Expression vectors and host cells expressing the heme enzymes are also provided by the present invention.Type: ApplicationFiled: February 20, 2014Publication date: August 28, 2014Applicant: California Institute of TechnologyInventors: Pedro S. Coelho, Eric M. Brustad, Frances H. Arnold, Zhan Wang, Jared C. Lewis
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Patent number: 8802401Abstract: The disclosure relates to engineered P450 polypeptides and use of such polypeptides in chemoenzymatic methods to construct selectively protected carbohydrates, which are useful as building blocks for preparation of carbohydrate derivatives and oligosaccharidesType: GrantFiled: June 18, 2008Date of Patent: August 12, 2014Assignees: The California Institute of Technology, The Scripps Research InstituteInventors: Frances H. Arnold, Chi-Huey Wong, Yuuichi Mitsuda, Michael M. Chen, Clay Bennett, William Greenberg, Jared Crawford Lewis, Sabine Bastian
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Patent number: 8741616Abstract: Cytochrome P450 BM-3 from Bacillus megaterium was engineered using a combination of directed evolution and site-directed mutagenesis to hydroxylate linear alkanes regio- and enantioselectively using atmospheric dioxygen as an oxidant. Mutant 9-10A-A328V hydroxylates octane primarily at the 2-positio to form S-2-octanol (40% ee). Another mutant, 1-12G, hydroxylates alkanes larger than hexane primarily at the 2-position, but forms R-2-alcohols (40-55% ee). These biocatalysts are highly active for alkane substrates and support thousands of product turnovers. These regio- and enantio-selectivities are retained in whole-cell biotransformations with E. coli, where the engineered P450s can be expressed at high levels and the expensive cofactor is supplied endogenously.Type: GrantFiled: November 9, 2012Date of Patent: June 3, 2014Assignee: California Institute of TechnologyInventors: Frances H. Arnold, Matthew W. Peters, Peter Meinhold
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Patent number: 8722371Abstract: Nucleic acids encoding cytochrome P450 variants are provided. The cytochrome P450 variants of have a higher alkane-oxidation capability, alkene-oxidation capability, and/or a higher organic-solvent resistance than the corresponding wild-type or parent cytochrome P450 enzyme. A preferred wild-type cytochrome P450 is cytochrome P450 BM-3. Preferred cytochrome P450 variants include those having an improved capability to hydroxylate alkanes and epoxidate alkenes comprising less than 8 carbons, and have amino acid substitutions corresponding to V78A, H236Q, and E252G of cytochrome P450 BM-3. Preferred cytochrome P450 variants also include those having an improved hydroxylation activity in solutions comprising co-solvents such as DMSO and THF, and have amino acid substitutions corresponding to T235A, R471A, E494K, and S1024E of cytochrome P450 BM-3.Type: GrantFiled: January 25, 2013Date of Patent: May 13, 2014Assignee: California Institute of TechnologyInventors: Edgardo T. Farinas, Frances H. Arnold, Ulrich Schwaneberg, Anton Blieder
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Patent number: 8603949Abstract: The present disclosure teaches that the recombination of homologous sequences of P450 enzymes, with the aid of SCHEMA to predict a resulting protein structure, is able to generate libraries of chimeras with significant functional diversity. Additionally, the members of these libraries demonstrate superior or unexpected new properties, which correlate with other factors that are observable in the library. Thus, the making of libraries of optimized P450 enzymes, the analysis of libraries to identify an optimized subset, and the optimized chimeras with improved or altered functionalities are all taught in the present disclosure.Type: GrantFiled: June 15, 2004Date of Patent: December 10, 2013Assignee: California Institute of TechnologyInventors: Frances H. Arnold, Christopher R. Otey
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Publication number: 20130288324Abstract: Nucleic acids encoding cytochrome P450 variants are provided. The cytochrome P450 variants of have a higher alkane-oxidation capability, alkene-oxidation capability, and/or a higher organic-solvent resistance than the corresponding wild-type or parent cytochrome P450 enzyme. A preferred wild-type cytochrome P450 is cytochrome P450 BM-3. Preferred cytochrome P450 variants include those having an improved capability to hydroxylate alkanes and epoxidate alkenes comprising less than 8 carbons, and have amino acid substitutions corresponding to V78A, H236Q, and E252G of cytochrome P450 BM-3. Preferred cytochrome P450 variants also include those having an improved hydroxylation activity in solutions comprising co-solvents such as DMSO and THF, and have amino acid substitutions corresponding to T235A, R471A, E494K, and S1024E of cytochrome P450 BM-3.Type: ApplicationFiled: January 25, 2013Publication date: October 31, 2013Applicant: THE CALIFORNIA INSTITUTE OF TECHNOLOGYInventors: Edgardo Farinas, Frances H. Arnold, Ulrich Schwaneberg, Anton Glieder
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Patent number: 8367386Abstract: Nucleic acids encoding cytochrome P450 variants are provided. The cytochrome P450 variants of have a higher alkane-oxidation capability, alkene-oxidation capability, and/or a higher organic-solvent resistance than the corresponding wild-type or parent cytochrome P450 enzyme. A preferred wild-type cytochrome P450 is cytochrome P450 BM-3. Preferred cytochrome P450 variants include those having an improved capability to hydroxylate alkanes and epoxidate alkenes comprising less than 8 carbons, and have amino acid substitutions corresponding to V78A, H236Q, and E252G of cytochrome P450 BM-3. Preferred cytochrome P450 variants also include those having an improved hydroxylation activity in solutions comprising co-solvents such as DMSO and THF, and have amino acid substitutions corresponding to T235A, R471A, E494K, and S1024E of cytochrome P450 BM-3.Type: GrantFiled: December 12, 2011Date of Patent: February 5, 2013Assignee: California Institute of TechnologyInventors: Edgardo Farinas, Frances H. Arnold, Ulrich Schwaneberg, Anton Glieder
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Patent number: 8361769Abstract: Cytochrome P450 CYP153A6 from Myobacterium sp. strain HXN1500 was engineered using in-vivo directed evolution to hydroxylate small-chain alkanes regioselectively. Mutant CYP153A6-BMO1 selectively hydroxylates butane and pentane at the terminal carbon to form 1-butanol and 1-pentanol, respectively, at rates greater than wild-type CYP153A6 enzymes. This biocatalyst is highly active for small-chain alkane substrates and the regioselectivity is retained in whole-cell biotransformations.Type: GrantFiled: November 16, 2009Date of Patent: January 29, 2013Assignee: U.S. Department of EnergyInventors: Daniel J. Koch, Frances H. Arnold
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Patent number: 8343744Abstract: Cytochrome P450 BM-3 from Bacillus megaterium was engineered using a combination of directed evolution and site-directed mutagenesis to hydroxylate linear alkanes regio- and enantioselectively using atmospheric dioxygen as an oxidant. Mutant 9-10A-A328V hydroxylates octane primarily at the 2-position to form S-2-octanol (40% ee). Another mutant, 1-12G, hydroxylates alkanes larger than hexane primarily at the 2-position, but forms R-2-alcohols (40-55% ee). These biocatalysts are highly active for alkane substrates and support thousands of product turnovers. These regio- and enantio-selectivities are retained in whole-cell biotransformations with E. coli, where the engineered P450s can be expressed at high levels and the expensive cofactor is supplied endogenously.Type: GrantFiled: January 3, 2011Date of Patent: January 1, 2013Assignee: The California Institute of TechnologyInventors: Frances H Arnold, Matthew W Peters, Peter Meinhold
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Patent number: 8309333Abstract: AlkB from Pseudomonas putida was engineered using in-vivo directed evolution to hydroxylate small chain alkanes. Mutant AlkB-BMO1 hydroxylates propane and butane at the terminal carbon at a rate greater than the wild-type to form 1-propanol and 1-butanol, respectively. Mutant AlkB-BMO2 similarly hydroxylates propane and butane at the terminal carbon at a rate greater than the wild-type to form 1-propanol and 1-butanol, respectively. These biocatalysts are highly active for small chain alkane substrates and their regioselectivity is retained in whole-cell biotransformations.Type: GrantFiled: November 16, 2009Date of Patent: November 13, 2012Assignee: The United States of America, as represented by Department of EnergyInventors: Daniel J. Koch, Frances H. Arnold
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Patent number: 8252559Abstract: A method and system for selectively fluorinating organic molecules on a target site wherein the target site is activated and then fluorinated are shown together with a method and system for identifying a molecule having a biological activity.Type: GrantFiled: February 4, 2009Date of Patent: August 28, 2012Assignee: The California Institute of TechnologyInventors: Rudi Fasan, Frances H. Arnold
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Publication number: 20120184015Abstract: Nucleic acids encoding cytochrome P450 variants are provided. The cytochrome P450 variants of have a higher alkane-oxidation capability, alkene-oxidation capability, and/or a higher organic-solvent resistance than the corresponding wild-type or parent cytochrome P450 enzyme. A preferred wild-type cytochrome P450 is cytochrome P450 BM-3. Preferred cytochrome P450 variants include those having an improved capability to hydroxylate alkanes and epoxidate alkenes comprising less than 8 carbons, and have amino acid substitutions corresponding to V78A, H236Q, and E252G of cytochrome P450 BM-3. Preferred cytochrome P450 variants also include those having an improved hydroxylation activity in solutions comprising co-solvents such as DMSO and THF, and have amino acid substitutions corresponding to T235A, R471A, E494K, and S1024E of cytochrome P450 BM-3.Type: ApplicationFiled: December 12, 2011Publication date: July 19, 2012Applicant: THE CALIFORNIA INSTITUTE OF TECHNOLOGYInventors: Edgardo T. Farinas, Frances H. Arnold, Ulrich Schwaneberg, Anton Glieder
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Publication number: 20120171693Abstract: The disclosure provides methods for identifying and producing stabilized chimeric proteins.Type: ApplicationFiled: January 5, 2008Publication date: July 5, 2012Applicant: THE CALIFORNIA INSTITUTE OF TECHNOLOGYInventors: Frances H. Arnold, Yougen Li
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Publication number: 20110319294Abstract: The present disclosure relates to CBH I chimera fusion polypeptides, nucleic acids encoding the polypeptides, and host cells for producing the polypeptides.Type: ApplicationFiled: June 1, 2011Publication date: December 29, 2011Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGYInventors: Frances H. Arnold, Pete Heinzelman
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Patent number: 8076114Abstract: Nucleic acids encoding cytochrome P450 variants are provided. The cytochrome P450 variants of have a higher alkane-oxidation capability, alkene-oxidation capability, and/or a higher organic-solvent resistance than the corresponding wild-type or parent cytochrome P450 enzyme. A preferred wild-type cytochrome P450 is cytochrome P450 BM-3. Preferred cytochrome P450 variants include those having an improved capability to hydroxylate alkanes and epoxidate alkenes comprising less than 8 carbons, and have amino acid substitutions corresponding to V78A, H236Q, and E252G of cytochrome P450 BM-3. Preferred cytochrome P450 variants also include those having an improved hydroxylation activity in solutions comprising co-solvents such as DMSO and THF, and have amino acid substitutions corresponding to T235A, R471A, E494K, and S1024E of cytochrome P450 BM-3.Type: GrantFiled: April 5, 2010Date of Patent: December 13, 2011Assignee: California Institute of TechnologyInventors: Edgardo T Farinas, Frances H. Arnold, Ulrich Schwaneberg, Anton Glieder
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Publication number: 20110244537Abstract: Cytochrome P450 BM-3 from Bacillus megaterium was engineered using a combination of directed evolution and site-directed mutagenesis to hydroxylate linear alkanes regio- and enantioselectively using atmospheric dioxygen as an oxidant. Mutant 9-10A-A328V hydroxylates octane primarily at the 2-position to form S-2-octanol (40% ee). Another mutant, 1-12G, hydroxylates alkanes larger than hexane primarily at the 2-position, but forms R-2-alcohols (40-55% ee). These biocatalysts are highly active for alkane substrates and support thousands of product turnovers. These regio- and enantio-selectivities are retained in whole-cell biotransformations with E. coli, where the engineered P450s can be expressed at high levels and the expensive cofactor is supplied endogenously.Type: ApplicationFiled: January 3, 2011Publication date: October 6, 2011Applicant: THE CALIFORNIA INSTITUTE OF TECHNOLOGYInventors: Frances H. Arnold, Matthew W. Peters, Peter Meinhold
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Patent number: 8026085Abstract: A method and system for selectively fluorinating organic molecules on a target site wherein the target site is activated and then fluorinated are shown together with a method and system for identifying a molecule having a biological activity.Type: GrantFiled: August 4, 2007Date of Patent: September 27, 2011Assignee: California Institute of TechnologyInventors: Rudi Fasan, Frances H. Arnold
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Publication number: 20110229872Abstract: The invention provides a microfabricated device for sorting cells based on a desired characteristic, for example, reporter-labeled cells can be sorted by the presence or level of reporter on the cells. The device includes a chip having a substrate into which is microfabricated at least one analysis unit. Each analysis unit includes a main channel, having a sample inlet channel, typically at one end, and a detection region along a portion of its length. Adjacent and downstream from the detection region, the main channel has a discrimination region or branch point leading to at least two branch channels. The analysis unit may further include additional inlet channels, detection points, branch points, and branch channels as desired. A stream containing cells is passed through the detection region, such that on average one cell occupies the detection region at a given time.Type: ApplicationFiled: November 24, 2010Publication date: September 22, 2011Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGYInventors: CHARLES F. SPENCE, ANNE Y. FU, STEPHEN R. QUAKE, FRANCES H. ARNOLD
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Patent number: 7863030Abstract: Cytochrome P450 BM-3 from Bacillus megaterium was engineered using a combination of directed evolution and site-directed mutagenesis to hydroxylate linear alkanes regio- and enantioselectively using atmospheric dioxygen as an oxidant. Mutant 9-10A-A328V hydroxylates octane primarily at the 2-positio to form S-2-octanol (40% ee). Another mutant, 1-12G, hydroxylates alkanes larger than hexane primarily at the 2-position, but forms R-2-alcohols (40-55% ee). These biocatalysts are highly active for alkane substrates and support thousands of product turnovers. These regio- and enantio-selectivities are retained in whole-cell biotransformations with E. coli, where the engineered P450s can be expressed at high levels and the expensive cofactor is supplied endogenously.Type: GrantFiled: April 15, 2009Date of Patent: January 4, 2011Assignee: The California Institute of TechnologyInventors: Frances H Arnold, Matthew W Peters, Peter Meinhold
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Publication number: 20100304464Abstract: The present disclosure relates to CBH II chimera fusion polypeptides, nucleic acids encoding the polypeptides, and host cells for producing the polypeptides.Type: ApplicationFiled: March 12, 2010Publication date: December 2, 2010Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGYInventors: Frances H. Arnold, Pete Heinzelman, Jeremy Minshull, Sridhar Govindarajan, Alan Villalobos