Abstract: Methods of providing shuffling libraries that include codon-varied oligonucleotide sequences are described. Codon-varied oligonucleotides are synthesized using trinucleotide or mononucleotide phosphoramidite sequences, and are derived from homologous or non-homologous nucleic acid sequences, or combinations of such sequences. Various methods of recombining codon-varied oligonucleotide sequences to expedite artificial evolution are also described. The present invention additionally relates to various integrated systems that are optionally used to automate these recombination methods.
Type:
Grant
Filed:
September 28, 1999
Date of Patent:
August 20, 2002
Assignee:
Maxygen, Inc.
Inventors:
Mark Welch, Jon Ness, Claes Gustafsson, Willem P. C. Stemmer, Jeremy Minshull
Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.
Type:
Grant
Filed:
December 22, 1998
Date of Patent:
August 6, 2002
Assignee:
Caliper Technologies Corp.
Inventors:
John Wallace Parce, Anne Kopf-Sill, Luc J. Bousse
Abstract: Methods of recombining nucleic acids, including homologous nucleic acids, are provided. Families of gene shuffling oligonucleotides and their use in recombination procedures, as well as polymerase and ligase mediated recombination methods are also provided.
Type:
Grant
Filed:
July 27, 2000
Date of Patent:
July 30, 2002
Assignee:
MaxyGen, Inc.
Inventors:
Andreas Crameri, Willem P. C. Stemmer, Jeremy Minshull, Steven H. Bass, Mark Welch, Jon E. Ness, Claes Gustafsson, Phillip A. Patten
Abstract: Methods of recombining nucleic acids, including homologous nucleic acids, are provided. Families of gene shuffling oligonucleotides and their use in recombination procedures, as well as polymerase and ligase mediated recombination methods are also provided.
Type:
Grant
Filed:
July 27, 2000
Date of Patent:
July 23, 2002
Assignee:
Maxygen, Inc.
Inventors:
Andreas Crameri, Willem P. C. Stemmer, Jeremy Minshull, Steven H. Bass, Mark Welch, Jon E. Ness, Claes Gustafsson, Phillip A. Patten
Abstract: The invention relates to the fabrication and use of biosensors comprising a plurality of optical fibers each fiber having attached to its “sensor end” biological “binding partners” (molecules that specifically bind other molecules to form a binding complex such as antibody-antigen, lectin-carbohydrate, nucleic acid-nucleic acid, biotin-avidin, etc.). The biosensor preferably bears two or more different species of biological binding partner. The sensor is fabricated by providing a plurality of groups of optical fibers. Each group is treated as a batch to attach a different species of biological binding partner to the sensor ends of the fibers comprising that bundle. Each fiber, or group of fibers within a bundle, may be uniquely identified so that the fibers, or group of fibers, when later combined in an array of different fibers, can be discretely addressed. Fibers or groups of fibers are then selected and discretely separated from different bundles.
Type:
Grant
Filed:
August 17, 2000
Date of Patent:
July 9, 2002
Assignees:
The Regents of the University of California, Medical Research Council
Inventors:
Daniel Pinkel, Joe Gray, Donna G. Albertson
Abstract: This invention pertains to the discovery that inhibition of phosphatidylinositol 3-kinase (PI3K) in human fetal undifferentiated cells induces morphological and functional endocrine differentiation. This is associated with an increase in mRNA levels of insulin, glucagon, and somatostatin, as well as an increase in the insulin protein content and secretion response to secretagogues. Blockade of PI3K also increases the proportion of pluripotent precursor cells coexpressing multiple hormones and the total number of terminally differentiated cells originating from these precursor cells.
Type:
Grant
Filed:
May 26, 1999
Date of Patent:
July 2, 2002
Assignee:
The Regents of the University of California
Inventors:
Andrezej Ptasznik, Alberti Hayek, Gillian M. Beattie
Abstract: Methods of modulating, tuning and improving hybridization properties and recombination properties of molecules for use in nucleic acid shuffling procedures, relates recombination mixtures and methods of modulating, tuning, improving and evolving splicing of RNAs and proteins are provided.
Type:
Grant
Filed:
November 27, 2000
Date of Patent:
July 2, 2002
Assignee:
Maxygen, Inc
Inventors:
Phillip A. Patten, Volker Heinrichs, Willem P. C. Stemmer
Abstract: The present invention provides a method for purifying follicle stimulating hormone (FSH) from biological samples, for example, from human pituitary glands or human postmenopausal urine, wherein the FSH is contaminated with other proteins, by use of dye-ligand affinity chromatography (DAC). Depending on the starting material used and the initial purity of FSH in the starting material, additional purification steps may be employed. These steps preferably involve the use of hydrophobic interaction chromatography. This process may be used to generate affinity pure FSH suitable for therapeutic applications. The methods of the invention provide high purity FSH with high overall yield. A further advantage is the ability to easily regenerate the chromatography media for re-use, thus providing added economy to the purification process.
Abstract: Microfluidic devices are provided for the performance of chemical and biochemical analyses, syntheses and detection. The devices of the invention combine precise fluidic control systems with microfabricated polymeric substrates to provide accurate, low cost miniaturized analytical devices that have broad applications in the fields of chemistry, biochemistry, biotechnology, molecular biology and numerous other fields.
Type:
Grant
Filed:
September 19, 2000
Date of Patent:
June 25, 2002
Assignee:
Caliper Technologies Corp.
Inventors:
John Wallace Parce, Michael R. Knapp, Calvin Y. H. Chow, Luc Bousse
Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.
Type:
Grant
Filed:
July 1, 1999
Date of Patent:
June 18, 2002
Assignee:
Caliper Technologies Corp.
Inventors:
John Wallace Parce, Anne R. Kopf-Sill, Luc J. Bousse
Abstract: Integrated systems, apparatus, software, and methods for performing biochemical analysis, including DNA sequencing, genomic screening, purification of nucleic acids and other biological components and drug screening are provided. Microfluidic devices, systems and methods for using these devices and systems for performing a wide variety of fluid operations are provided. The devices and systems of are used in performing fluid operations which require a large number of iterative, successive or parallel fluid manipulations, in a microscale, or sealed and readily automated format.
Type:
Grant
Filed:
November 20, 2000
Date of Patent:
June 18, 2002
Assignee:
Caliper Technologies Corp.
Inventors:
Michael Knapp, John Wallace Parce, Luc J. Bousse, Anne R. Kopf-Sill
Abstract: Methods are provided for the evolution of proteins of industrial and pharmaceutical interest, including methods for effecting recombination and selection. Compositions produced by these methods are also disclosed.
Type:
Grant
Filed:
November 22, 2000
Date of Patent:
June 18, 2002
Assignee:
Maxygen, Inc.
Inventors:
Phillip A. Patten, Willem P. C. Stemmer
Abstract: Methods and compositions for treatment of animal feed or silage by treatment with a mixed culture of heterofermentive lactic acid bacteria and homofermentive lactic acid bacteria of the proper ratio. Bacterial strains for such treatment are also provided.
Type:
Grant
Filed:
November 3, 2000
Date of Patent:
June 11, 2002
Assignee:
Pioneer Hi-Bred International, Inc.
Inventors:
Russell Kuo-fu Chan, Scott Dennis, Elizabeth K. Harman, William Rutherford, Brenda Smiley
Abstract: A method for DNA reassembly after random fragmentation, and its application to mutagenesis of nucleic acid sequences by in vitro or in vivo recombination is described. In particular, a method for the production of nucleic acid fragments or polynucleotides encoding mutant proteins is described. The present invention also relates to a method of repeated cycles of mutagenesis, shuffling and selection which allow for the directed molecular evolution in vitro or in vivo of proteins.
Abstract: Integrated systems, apparatus, software, and methods for performing biochemical analysis, including DNA sequencing, genomic screening, purification of nucleic acids and other biological components and drug screening are provided. Microfluidic devices, systems and methods for using these devices and systems for performing a wide variety of fluid operations are provided. The devices and systems of are used in performing fluid operations which require a large number of iterative, successive or parallel fluid manipulations, in a microscale, or sealed and readily automated format.
Type:
Grant
Filed:
June 27, 2000
Date of Patent:
May 21, 2002
Assignee:
Caliper Technologies Corp.
Inventors:
Michael Knapp, John Wallace Parce, Luc J. Bousse, Anne R. Kopf-Sill
Abstract: The present invention is generally directed to the evolution of new metabolic pathways and the enhancement of bioprocessing through a process herein termed recursive sequence recombination. Recursive sequence recombination entails performing iterative cycles of recombination and screening or selection to “evolve” individual genes, whole plasmids or viruses, multigene clusters, or even whole genomes. Such techniques do not require the extensive analysis and computation required by conventional methods for metabolic engineering.
Abstract: The present invention provides heregulin variants that are capable of binding an ErbB receptor. Included in the invention are variants of human heregulins, and, in particular, variants of human heregulin-&bgr;1 having enhanced affinity for the ErbB-3 and ErbB-4 receptors. These variants include at least one amino acid substitution and can include further modifications. The invention also provides nucleic acid molecules encoding heregulin variants and related vectors, host cells, pharmaceutical compositions, and methods.
Type:
Grant
Filed:
July 17, 1998
Date of Patent:
May 14, 2002
Assignee:
Genentech, Inc.
Inventors:
Marcus D. Ballinger, Jennifer T. Jones, Wayne J. Fairbrother, Mark X. Sliwkowski, James A. Wells
Abstract: Ultrasonic energy in the form of guided waves is launched into the wall of a fluid-filled container. The guided wave propagates around the circumference of the container from a transmitting transducer to a receiving transducer. Part of the guide wave energy leaks into the fluid in the form of bulk waves, reflects off the inner wall on the other side and enters back to the receiving transducer trailing the direct wave. Analysis of the received waves determines the presence of corrosion pitting and MIC nodules on the container inner wall, and fluid level. In addition, it determines whether foreign objects are inside the container. The guided waves are created with wideband transducers excited at certain frequencies that depend on the material and geometry of the part being measured. The leakage energy is maximized with a shaped tone burst pulse at the specified frequency.
Type:
Grant
Filed:
July 11, 2000
Date of Patent:
April 9, 2002
Assignee:
Digital Wave Corporation
Inventors:
Michael R. Gorman, Steven M. Ziola, Wei Huang
Abstract: Ultrasonic energy in the form of guided waves (plate waves or Lamb waves) is launched into the wall of a container. The guided wave propagates around the circumference of the container from a transmitting transducer to a receiving transducer. Analysis of the received waves determines the presence of corrosion pitting and MIC nodules on the container inner wall, as well as the existence of foreign objects in intimate contact with the container wall. The guided waves are created with wideband transducers excited at certain frequencies that depend on the material and geometry of the part being measured. The guided wave ultrasonic energy is maximized with a shaped tone burst pulse at the specified frequency rather than an electrical spike commonly used to excite transducers in standard ultrasonic search units.