Patents Assigned to Molecular Probes, Inc.
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Patent number: 6399392Abstract: The quenching compounds of the invention are nitrogen-substituted xanthenes that are substituted by one or more aromatic or heteroaromatic quenching moieties. The quenching compounds of the invention exhibit little or no observable fluorescence and efficiently quench a broad spectrum of luminescent compounds. The chemically reactive quenching compounds possess utility for labeling a wide variety of substances, including biomolecules. These labeled substances are highly useful for a variety of energy-transfer assays and applications.Type: GrantFiled: April 21, 2000Date of Patent: June 4, 2002Assignee: Molecular Probes, Inc.Inventors: Richard P. Haugland, Victoria L. Singer, Stephen T. Yue
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Publication number: 20020064794Abstract: Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens.Type: ApplicationFiled: October 1, 2001Publication date: May 30, 2002Applicant: MOLECULAR PROBES, INC.Inventors: Wai-Yee Leung, Ching-Ying Cheung, Stephen Yue
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Patent number: 6329205Abstract: The invention relates to the staining of amine-containing polymers, including including peptides, polypeptides, and proteins, in gels and on solid supports, using complexes of europium (3+).Type: GrantFiled: August 30, 2000Date of Patent: December 11, 2001Assignee: Molecular Probes, Inc.Inventors: Zhenjun Diwu, Wayne F. Patton
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Patent number: 6323186Abstract: The invention relates to dipyrrometheneboron difluoride-substituted nucleotides substituted by a dipyrrometheneboron difluoride label on a phosphate moiety. The nucleotides of the invention are useful in fluorescence assays, including protein binding assays and assays for hydrolase enzymes.Type: GrantFiled: September 18, 2000Date of Patent: November 27, 2001Assignees: Molecular Probes, Inc., Thomas Jefferson UniversityInventors: Dieter H. Klaubert, Kyle R. Gee, Charles M. Brenner
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Patent number: 6323337Abstract: The invention relates to oligonucleotides labeled with an energy transfer acceptor useful in conjunction with fluorescent nucleic acid stains. The resulting oligonucleotides are useful for decreasing background fluorescence during amplification assays and in ligation assays, and for detecting hybridization.Type: GrantFiled: May 12, 2000Date of Patent: November 27, 2001Assignee: Molecular Probes, Inc.Inventors: Victoria L. Singer, Richard P. Haugland
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Patent number: 6316267Abstract: The invention relates to the staining of poly(amino acids), including peptides, polypeptides and proteins in gels and on solid supports, using neutral or anionic complexes of transition metals.Type: GrantFiled: October 27, 1999Date of Patent: November 13, 2001Assignee: Molecular Probes, Inc.Inventors: Mahesh K. Bhalgat, Zhenjun Diwu, Richard P. Haugland, Wayne F. Patton
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Patent number: 6291203Abstract: The present invention relates to the use of positively-charged unsymmetrical cyanine dyes, including novel unsymmetrical cyanine dyes, to stain cells and selectively stain intracellular organelles, with particular advantages in staining mitochondria. The dyes are generally weakly fluorescent in aqueous solution but highly fluorescent in cells and organelles, typically staining cells or mitochondria with a green fluorescence. The dyes stain mitochondria in both live and dead cells, and are retained in mitochondria even where the cells are treated with solvents that permeabilize cell and mitochondrial membranes. Mitochondria or cells stained according to this method are optionally stained with an additional detection reagent, such as a labeled antibody, labeled oligonucleotide, fluorogenic enzyme substrate, or other indicator for a specific cellular component or substructure, including another unsymmetrical cyanine stain of the same or different class.Type: GrantFiled: December 3, 1998Date of Patent: September 18, 2001Assignee: Molecular Probes, Inc.Inventors: Martin Poot, Fei Mao
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Patent number: 6265179Abstract: Inorganic phosphate may be detected and optionally quantified via the coupling of a phosphate-dependent enzymatic reaction with an enzyme system that generates hydrogen peroxide in the presence of a chromogenic or fluorogenic peroxidase substrate. Phosphate consuming or phosphate-producing enzymes or their substrates may also be detected and/or quantified, including pyrophosphatase enzymes or pyrophosphatase.Type: GrantFiled: February 1, 2000Date of Patent: July 24, 2001Assignee: Molecular Probes, Inc.Inventors: Mingjie Zhou, Richard P. Haugland
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Patent number: 6229055Abstract: Facile syntheses for fluorinated resorcinol and aminophenol derivatives are provided that yield isomer-free products in good yield. These novel methods use generally available precursors and standard laboratory reagents and equipment to reproducibly produce these synthetically useful reagents in relatively large quantities. The resulting fluorinated resorcinols and aniinophenols possess utility in the preparation of fluorinated fluorescein and rhodol dyes.Type: GrantFiled: August 3, 2000Date of Patent: May 8, 2001Assignee: Molecular Probes, Inc.Inventors: Dieter H. Klaubert, Kyle R. Gee
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Patent number: 6162931Abstract: The family of dyes of the invention are fluoresceins and rhodols that are directly substituted on one or more aromatic carbons by fluorine. These fluorine-substituted fluorescent dyes possess greater photostability and have lower sensitivity to pH changes in the physiological range of 6-8 than do non-fluorinated dyes, exhibit less quenching when conjugated to a substance, and possess additional advantages. The dyes of the invention are useful as detectable tracers and for preparing conjugates of organic and inorganic substances.Type: GrantFiled: April 12, 1996Date of Patent: December 19, 2000Assignee: Molecular Probes, Inc.Inventors: Kyle R. Gee, Martin Poot, Dieter H. Klaubert, Wei-Chuan Sun, Richard P. Haugland, Fei Mao
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Patent number: 6130101Abstract: The present invention describes xanthene dyes, including rhodamines, rhodols and fluoresceins that are substituted one or more times by a sulfonic acid or a salt of a sulfonic acid. The dyes of the invention, including chemically reactive dyes and dye-conjugates are useful as fluorescent probes, particularly in biological samples.Type: GrantFiled: September 23, 1997Date of Patent: October 10, 2000Assignee: Molecular Probes, Inc.Inventors: Fei Mao, Wai-Yee Leung, Richard P. Haugland
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Patent number: 6013802Abstract: The present invention describes a family of fluorescent indicators for metal cations. The indicators are fluorophore conjugates of pyridyl-based metal ion chelators. The indicators are very sensitive detection as quantification reagents for a variety of metals, in a variety of oxidation states, even in the presence of high concentrations of Ca.sup.2+, Na.sup.+, or K.sup.+ or other ions, such as is found in seawater, making them highly useful for assaying physiological samples, biological samples, or environmental samples.Type: GrantFiled: February 7, 1997Date of Patent: January 11, 2000Assignee: Molecular Probes, Inc.Inventors: Brian Matthew Hoyland, Michael A. Kuhn, Richard P. Haugland
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Patent number: 6004536Abstract: The present invention relates to a family of cyanine dyes possessing lipophilic alkyl chains and either one or more reactive functional groups, bromo or chloro, or phenyl, sulfophenyl or polysulfophenyl substituents or combinations thereof. The dyes of the invention are useful for staining membranes in cells or isolated from cells, and are well-retained therein. Additionally, the reactive dyes of the invention are useful for preparing dye-conjugates, thereby conferring the membrane staining ability of the subject dye onto the resulting dye-conjugate.Type: GrantFiled: August 14, 1996Date of Patent: December 21, 1999Assignee: Molecular Probes, Inc.Inventors: Wai-Yee Leung, Richard P. Haugland, Fei Mao
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Patent number: 6005113Abstract: The invention relates to fluorescent dyes that are substituted or unsubstituted derivatives of 1-(isoindolyl)methylene-isoindole that are bound through both isoindole nitrogens to a boron difluoride moiety, forming a fluorescent dibenzopyrrometheneboron difluoride compound ##STR1## that is further substituted by bathochromic substituents that are aryl or heteroaryl moieties further substituted by an additional aryl or heteroaryl, that is itself optionally further substituted by an additional aryl or heteroaryl. These aryl and heteroaryl groups are separated by a covalent bond, or by an ethenyl, butadienyl or hexatrienyl linkage. The dyes of the invention are particularly useful as labels for carriers, particularly polymeric microparticles. The resulting microparticles have a long-wavelength fluorescence emission, and possess utility for tracing flow in biological systems, particularly in tracing blood flow.Type: GrantFiled: May 14, 1997Date of Patent: December 21, 1999Assignee: Molecular Probes, Inc.Inventors: Yexin Wu, Dieter H. Klaubert, Hee Chol Kang, Yu-Zhong Zhang
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Patent number: 5888829Abstract: The present invention describes a family of photolabile caged ionophores. The compounds of the present invention are photolytically cleavable esters of nigericin, ionomycin, A-23187, 4-Br-A-23187 and monensin. The photolysis of the present compounds allows the release of the free ionophore in vivo or in vitro with precise spatial and temporal control. The compounds are useful in the study of ion transport and control in cells and across membranes.Type: GrantFiled: April 26, 1996Date of Patent: March 30, 1999Assignee: Molecular Probes, Inc.Inventors: Kyle R. Gee, Paul J. Millard
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Patent number: 5872243Abstract: The present invention describes a family of photolabile caged nucleotides, including cyclic nucleotides. The compounds of the present invention are caged analogs and derivatives of NAD.sup.+, NADH, NADP, NADPH, NAADP and cADPR. The photolysis of the present compounds allows the release of the free nucleotide in vivo or in vitro with precise spatial and temporal control. The compounds are useful for the photolytic generation of free nucleotides in aqueous samples, for example, in the study of calcium mobilization in cells and cell homogenates.Type: GrantFiled: June 30, 1995Date of Patent: February 16, 1999Assignees: Molecular Probes, Inc., The Regents of the University of MinnesotaInventors: Kyle R. Gee, Hon Cheung Lee, Robert Aarhus, Richard P. Haugland, Timothy F. Walseth, Richard M. Graeff
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Patent number: 5869689Abstract: Dipyrrometheneboron difluoride dyes possessing a covalently attached basic amine moiety are described that have utility for staining acidic organelles. Samples comprising isolated acidic organelles, or a cell or cells containing acidic organelles, are stained by preparing an aqueous labeling solution of the dye and incubating the sample in the labeling solution for a time sufficient to produce fluorescent labeled acidic organelles.Type: GrantFiled: October 17, 1995Date of Patent: February 9, 1999Assignee: Molecular Probes, IncInventors: Yu-Zhong Zhang, Zhenjun Diwu, Richard P. Haugland
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Patent number: 5863753Abstract: The invention comprises cyanine dyes, in particular chemically reactive dyes, conjugates of reactive cyanine dyes, the non-covalent complexes of nucleic acids with the dyes and dye-conjugates of the invention, and a method of forming a nucleic acid complex with the dyes and dye-conjugates of the present invention. The dyes of the invention are useful for the preparation of dye-conjugates. The presence of a reactive group on the unsymmetrical cyanine dyes of the invention facilitates their covalent conjugation to a variety of substances, both biological and synthetic.Type: GrantFiled: August 19, 1997Date of Patent: January 26, 1999Assignee: Molecular Probes, Inc.Inventors: Richard P. Haugland, Victoria L. Singer, Stephen T. Yue, Paul J. Millard
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Patent number: 5846737Abstract: The invention describes useful conjugates of sulforhodamine, wherein the conjugated substance and the fluorophore are separated by an alkanoic acid spacer that is attached to the fluorophore via a sulfonamide bond. The increased length of the covalent linkage due to the spacer results in dye-conjugates having a number of surprisingly advantageous properties relative to previous sulforhodamine-labeled conjugates, including increased fluorescence.Type: GrantFiled: July 26, 1996Date of Patent: December 8, 1998Assignee: Molecular Probes, Inc.Inventor: Hee Chol Kang
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Patent number: 5830912Abstract: The present invention comprises 6,8-difluoro-7-hydroxycoumarins and derivatives of 6,8-difluoro-7-hydroxycoumarins, including reactive dyes, dye-conjugates and enzyme substrates. These fluorine-substituted fluorescent dyes typically possess greater photostability and lower pH sensitivity in the physiological pH range than their nonfluorinated analogs, exhibit less fluorescence quenching when conjugated to a substance, possess absorption and emission spectra that closely match those of their nonfluorinated analogs, and also exhibit higher quantum yields than their nonfluorinated analogs.Type: GrantFiled: November 15, 1996Date of Patent: November 3, 1998Assignee: Molecular Probes, Inc.Inventors: Kyle R. Gee, Richard P. Haugland, Wei-Chuan Sun