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Sequencing-related US Patents, Granted January — February 2007

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US Patent 7,173,125. Triphosphate oligonucleotide modification reagents and uses thereof. Inventor: David Schwartz, Richard Hogrefe. Assignee: None.
 
Protects hydrazino, oxyamino, and carbonyl-based monomers and methods for incorporation into oligonucleotides during enzymatic synthesis. The monomers “are readily incorporated into oligonucleotide chains, hence can be used in any application that involves or uses a nucleoside triphosphate, such as DNA and RNA sequencing, detecting, labeling and amplification methodologies,” according to the inventors.
 

 
US Patent 7,170,050. Apparatus and methods for optical analysis of molecules. Inventors: Stephen Turner, Jonas Korlach. Assignee: Pacific Biosciences.
 
Covers methods of preparing and using optical confinement arrays for analyzing molecules and/or monitoring chemical reactions. The apparatus and methods “are particularly useful for high-throughout and low-cost single-molecular analysis,” according to the inventors. The invention also covers kits containing the optical confinement arrays, which can differ depending on the intended use of the kit. “Where the kit is for DNA sequencing, the kit typically comprises: (a) an array of optical confinements, preferably zero-mode waveguides of the present invention that permits resolution of individual molecules present at a concentration higher than about 1 micromolar; (b) sequencing reagents typically including polymerases, aqueous buffers, salts, primers, and nucleoside triphosphates,” according to the patent.
 

 
US Patent 7,169,560. Short cycle methods for sequencing polynucleotides. Inventors: Stanley Lapidus, Philip Buzby, Timothy Harris. Assignee: Helicos BioSciences.
 
Protects methods for sequencing a polynucleotide comprising “stopping an extension cycle in a sequence by synthesis reaction before the reaction has run to near or full completion,” according to the patent abstract. The patent claims describe a method that includes exposing a nucleic acid template hybridized to a primer to a polymerase capable of catalyzing nucleotide addition to the primer, and a labeled nucleotide that is not a chain terminating nucleotide, “under reaction conditions and for a time such that on average only one nucleotide is added to said primer by said polymerase to produce an extended primer incorporating said labeled nucleotide.” The method then identifies the single labeled nucleotide, neutralizes the label, and repeats the process at least once. The sequence is determined based upon the order of incorporation of the labeled nucleotides. According to the inventors, the methods described in the patent “solve the problems that imaging systems have in accurately resolving a sequence at the single-molecule level” and “solve the problem of determining the number of nucleotides in a homopolymer stretch.”
 

 
US Patent 7,169,557. Universal nucleotides for nucleic acid analysis. Inventors: Barnett Rosenblum, Geun-Sook Jeon, Shaheer H. Khan. Assignee: Applera.
 
Covers methods and kits for making and analyzing primer extension products incorporating one or more universal bases, “including methods and kits for nucleic acid sequencing and microsatellite analysis,” according to the patent abstract.
 

 
US Patent 7,169,279. Sample handling system for a multi-channel capillary electrophoresis device. Inventors: Howard Gregg King, John Shigeura, Eric Nordman, Sean Matthew Desmond. Assignee: Applera.
 
Protects a sample-handling system in a multi-channel capillary electrophoresis apparatus that includes a work surface for supporting samples that are located at several work surface coordinates and a sample-loading assembly that includes loading wells. The system also includes a programmable sample transfer device for automatically transferring a sample from a work surface coordinate to a loading well, as well as methods for using the sample-handling system.
 

 
US Patent 7,169,276. Capillary electrophoresis method and apparatus for reducing peak broadening associated with the establishment of an electric field. Inventor: Ben Johnson, Eric Nordman. Assignee: Applera.
 
Protects methods for “reducing peak broadening associated with the establishment of a run field in a capillary electrophoresis process, and apparatus useful for carrying out such methods,” according to the patent abstract. Methods include “defining a maximum ramp rate to be used during an initial electric field ramp, defining a minimum period over which the run field is established, and/or maintaining a temperature of a separation medium to within certain ranges during the initial electric field ramp.”
 

 
US Patent 7,163,658. Rapid sequencing of polymers. Inventor: Rouvain Bension. Assignee: None.
 
Protects a method and device for sequencing “at least a fragment of a linear polymer,” according to the patent abstract. The device includes a well for placement of a rotaxane “comprising the combination of a cyclic molecule and a linear polymer threaded through said cyclic molecule.” The device also includes a probe with the ability to move the linear polymer relative to the cyclic molecule while producing a signal resulting from the interaction of the cyclic molecule and a unit attached to the polymer, as well as a means for reading the signal. “The device and method are especially useful for the sequencing of DNA,” the patent abstract states.
 

 
US Patent 7,157,230. Electron induced fluorescent method for nucleic acid sequencing. Inventor: Eric Hannah. Assignee: Intel.
 
Protects compositions and related methods for sequencing a target nucleic acid. In certain embodiments, the apparatus is a microfluidic apparatus including an input chamber, microchannel, output chamber, and a detection unit that is connected to the microchannel. In preferred embodiments, the methods include hybridizing a target nucleic acid to one or more probe libraries, moving the hybridized target nucleic acid past the detector, and detecting bound probes. The patent claims describe a method in which the target nucleic acid is hybridized to a probe library containing at least 256 distinguishably labeled different probes, wherein the probes are labeled with conductive polymers; separating the hybridized nucleic acid from unhybridized probes; and detecting the order of hybridized probes along the nucleic acid.

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