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Patents of Note: Jan 27, 2009

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US Patent 7,482,444. Terminating substrates for DNA polymerases
Inventor: Jari Hovinen
Assignee: Wallac Oy, Turku, Finland

Provides nucleoside 5'-triphosphates or their acylic analogues that are labeled with luminescent or non-luminescent lanthanide(III) chelates to serve as terminating substrates for DNA polymerases. Major advantages of the invention are that each DNA nucleobase is detected by its own metal chelate, so the base sequence can be analyzed by detecting the specific signal derived form the appropriate lanthanide chelate; and that the lanthanide(III) chelate can be either luminescent or non-luminescent.


US Patents 7,482,173 and 7,476,550. Method for attachment of silylated molecules to glass surfaces
Inventors: Viswanadham Garimella, Yasmith Bernal
Assignee: Nanosphere

Provides a method for the efficient immobilization of silylated molecules, such as silylated oligonucleotides or proteins, onto unmodified surfaces such as a glass surface. Also provided are compounds, devices, and kits for modifying surfaces such as glass surfaces.


US Patent 7,476,504. Use of reversible extension terminator in nucleic acid sequencing
Inventor: Stephen Turner
Assignee: Pacific Biosciences of California

Relates to the uses of reversible extension terminator in conjunction with optical confinements in nucleic acid sequencing. The methods presented eliminate the need for a washing step, and take advantage of the deferral of detection associated with reversible extension terminators. The apparatus and methods embodied in the invention are particularly useful for high-throughput and low-cost nucleic acid sequencing.


US Patent 7,476,503. Apparatus and method for performing nucleic acid analysis
Inventors: Stephen Turner, Jonas Korlach
Assignee: Pacific Biosciences of California

The invention relates to optical confinements, methods of preparing and methods of using them for analyzing molecules and/or monitoring chemical reactions. The apparatus and methods embodied in the present invention are particularly useful for high-throughput and low-cost single-molecular analysis.


US Patent 7,482,120. Methods and compositions for improving fidelity in a nucleic acid synthesis reaction
Inventor: Philip Richard Buzby
Assignee: Helicos Biosciences

Provides methods and compositions for improving the fidelity of a sequencing-by-synthesis reaction by using a nucleotide derivative that forms a hydrogen bond with a complementary nucleotide on a template, but fails to form a phosphodiester bond with the 3' hydroxyl group of a primer under conditions otherwise suitable for a polymerization reaction; thereby blocking incorporation of a mismatched nucleotide.


US Patent 7,476,734. Nucleotide analogs
Inventor: David Liu
Assignee: Helicos Biosciences

The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.

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US Patent 7,476,501. Methods and device for DNA sequencing using surface enhanced raman scattering (SERS)
Inventors: Selena Chan, Xing Su, Tae-Woong Koo
Assignee: Intel

Discloses methods and an apparatus for nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, exonuclease treatment of the nucleic acids results in the release of nucleotides. The nucleotides may pass from a reaction chamber through a microfluidic channel and enter a nanochannel or microchannel. The nanochannel or microchannel may be packed with nanoparticle aggregates containing hot spots for Raman detection. As the nucleotides pass through the nanoparticle hot spots, they may be detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS), and/or coherent anti-Stokes Raman spectroscopy (CARS). Identification of the sequence of nucleotides provides the nucleic acid sequence. Other embodiments of the invention concern apparatus for nucleic acid sequencing.


US Patent 7,470,517. Method for de novo detection of sequences in nucleic acids: target sequencing by fragmentation
Inventors: Charles Cantor, Fouad Siddiqi
Assignee: Trustees of Boston University

Provides a method for determining nucleic acid sequences of a template nucleic acid that requires no prior knowledge of the nucleic acid sequence. The method is based on combining information about the mass of a fragment, the mass of any one nucleotide and the combinations thereof, and the sequence specificity of a nucleotide cutter, either enzymatic or chemical cutter, to determine a sequence of a nucleic acid fragment. This method allows for de novo detection of sequences in a target nucleic acid without requiring any prior sequence information. This method is called partial sequencing by fragmentation (PSBF) and works by fragmenting a target into oligo- or polynucleotides whose masses or lengths are uniquely associated with known sequences. The identities of these sequences are determined solely by the specific fragmentation method, and are always independent of the target. PSBF can be implemented using electrophoresis, mass spectrometry, or any other method that can be used to distinguish the size of the cut nucleic acid sequence fragments.


US Patent 7,476,735. Compounds and methods for labeling oligonucleotides
Inventors: Andrei Laikhter, Joseph Walder, Mark Behlke, Mikhail Podyminogin, Yawful Yong
Assignee: Integrated DNA Technologies

Provides a novel method of labeling oligonucleotides, with reporter moieties, including, but not limited to, quenchers, fluorophores, biotin, digoxigenin, peptides, and proteins. In addition, the invention provides a method of detecting hybridization of oligonucleotides. This invention also provides novel azo quenchers, and compositions comprising labeled oligonucleotides and solid supports.


US Patent 7,468,243. 2-aminopyrimidin-4-one nucleic acid labeling compounds
Inventors: Glenn McGall, Anthony Barone
Assignee: Affymetrix

Discloses nucleic acid labeling compounds that are useful for attaching a detectable label to a nucleic acid.


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US Patent 7,465,578. Nucleic acid sequencing by Raman monitoring of uptake of precursors during molecular replication
Inventors: Andrew Berlin, Steven Kirch, Gabi Neubauer, Valluri Rao, Mineo Yamakawa
Assignee: Intel

Discloses methods, compositions, and apparatus for nucleic acid sequence determination. The methods involve isolation of one or more nucleic acid template molecules and polymerization of a nascent complementary strand of nucleic acid, using a DNA or RNA polymerase or similar synthetic reagent. As the nascent strand is extended one nucleotide at a time, the disappearance of nucleotide precursors from solution is monitored by Raman spectroscopy or FRET. The nucleic acid sequence of the nascent strand, and the complementary sequence of the template strand, may be determined by tracking the order of incorporation of nucleotide precursors during the polymerization reaction. Certain embodiments concern an apparatus comprising a reaction chamber and detection unit, of use in practicing the described methods. The methods, compositions, and apparatus are of use in sequencing very long nucleic acid templates in a single sequencing reaction.


US Patent 7,465,539. DNA polymerases with enhanced length of primer extension
Inventors: Wayne Barnes
Assignee: Takara Bio

Describes a formulation of thermostable or other DNA polymerases comprising (a) at least one thermostable or other DNA polymerase which lacks 3'-exonuclease activity, and (b) at least one thermostable DNA polymerase exhibiting 3'-exonuclease activity, where the ratio of (a) to (b) is greater than 1. Also provided is an improved method for enzymatic extension of DNA strands, especially while, but not limited to, amplifying nucleic acid sequences by polymerase chain reaction, where the mentioned formulation is made and used to catalyze primer extension.


US Patent 7,462,452. Field-switch sequencing
Inventors: John Williams, Jon Anderson
Assignee: Pacific Biosciences of California

Provides novel compositions, methods, and an apparatus for DNA sequencing that can be performed, for example, in a two-electrode chamber. The invention also provides a method for sequencing a nucleic acid comprising immobilizing several complexes consisting of a target nucleic acid, a primer nucleic acid, and a polymerase onto a surface, contacting the surface with several charged particles consisting of a nucleotide phosphate by applying an electric field, reversing the electric field to transport unbound charged particles away from the surface, and detecting the incorporation of a nucleotide phosphate into a single molecule of the primer nucleic acid.


US Patent 7,462,468. DNA intercalating agents and methods of use
Inventors: John Williams, Daniel Draney
Assignee: Pacific Biosciences of California

The invention provides compositions and methods for detecting incorporation of a labeled nucleotide triphosphate onto the growing end of a primer nucleic acid molecule. The method is used, for example, to genotype and sequence a nucleic acid. In a preferred embodiment, the method described detects individual NTP molecules.


US Patent 7,462,449. Methods and apparatuses for analyzing polynucleotide sequences
Inventor: Stephen Quake
Assignee: California Institute of Technology

Provides methods for high speed, high throughput analysis of polynucleotide sequences, and apparatuses with which to carry out the methods.

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