Patents by Inventor Roger Y. Tsien
Roger Y. Tsien 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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Patent number: 7431915Abstract: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.Type: GrantFiled: October 31, 2003Date of Patent: October 7, 2008Assignee: The Regents of the University of CaliforniaInventors: Tao Jiang, Roger Y. Tsien
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Patent number: 7427680Abstract: Fluorescent substrates for beta-lactamases having the general formula shown above are provided. Z includes a fluorophore or chromophore and includes a group that may link to the lactam-containing group; R1 and R2 are independently selected from H, aliphatic, aromatic, alkyl, and acyl; R4 may be H and lower alkyl; B may be H, physiologically acceptable salts or metal, ester groups, ammonium cations, —CHR5OCO(CH2)nCH3, —CHR5OCOC(CH3)3, acylthiomethyl, acyloxy-alpha-benz, deltabutyrolactonyl, methoxycarbonyloxymethyl, phenyl, methylsulphinylmethyl, beta-morpholinoethyl, dialkylaminoethyl, and dialkylaminocarbonyloxymethyl, in which R5 is selected from the group consisting of H and lower alkyl; n is an integer between 0 and 10, inclusive; and A may be S, O, SO, SO2 or CH2. In embodiments, the beta-lactam ring may be cleaved by a beta-lactamase enzyme effective to free a fluorophore.Type: GrantFiled: July 2, 2004Date of Patent: September 23, 2008Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Jianghong Rao
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Patent number: 7396926Abstract: Provided are fluorescent substrates for ?-lactamases having the general formula I: in which R is a benzyl, 2-thienylmethyl, or cyanomethyl group; R? is selected from the group consisting of H, physiologically acceptable salts or metal, ester groups, ammonium cations, —CHR2OCO(CH2)nCH3, —CHR2OCOC(CH3)3, acylthiomethyl, acyloxy-alpha-benzyl, deltabutyrolactonyl, methoxycarbonyloxymethyl, phenyl, methylsulphinylmethyl, ?-morpholinoethyl, dialkylaminoethyl, and dialkylaminocarbonyloxymethyl, in which R2 is selected from the group consisting of H and lower alkyl; A is selected from the group consisting of S, O, SO, SO2 and CH2; and Z is a donor fluorescent moiety. Also provided are methods of use of the compound of general formula I.Type: GrantFiled: January 11, 2002Date of Patent: July 8, 2008Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Jianghong Rao
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Patent number: 7393923Abstract: Methods using somatic hypermutation (SHM) for producing polypeptide and nucleic acid variants, and nucleic acids encoding such polypeptide variants are disclosed. Such variants may have desired properties. Also disclosed are novel polypeptides, such as improved fluorescent proteins, produced by the novel methods, and nucleic acids, vectors, and host cells comprising such vectors.Type: GrantFiled: November 8, 2004Date of Patent: July 1, 2008Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Lei Wang
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Patent number: 7332598Abstract: Non-oligomerizing fluorescent proteins, which are formed by operatively linking two or more monomers of a fluorescent protein, or which are derived from a fluorescent protein having at least one mutation that reduces or eliminates the ability of the fluorescent protein to oligomerize, are provided. The non-oligomerizing fluorescent proteins can be derived from a naturally occurring green fluorescent protein, a red fluorescent protein, or other fluorescent protein, or a fluorescent protein related thereto. Also provided is a fusion protein, which includes a non-oligomerizing fluorescent protein linked to at least one polypeptide of interest. In addition, a polynucleotide encoding a non-oligomerizing fluorescent protein is provided, as is a recombinant nucleic acid molecule, which includes polynucleotide encoding a non-oligomerizing fluorescent protein operatively linked to at least a second polynucleotide.Type: GrantFiled: July 6, 2004Date of Patent: February 19, 2008Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Robert E. Campbell
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Patent number: 7329735Abstract: The present invention relates generally to variant fluorescent proteins, and more specifically to monomeric and dimeric forms of Anthozoan fluorescent proteins. In one aspect, the present invention provides variants of fluorescent proteins, where the variants have a reduced propensity to tetramerize, and form dimeric or monomeric structures. The invention also relates to methods of making and using such fluorescent protein monomers and dimers.Type: GrantFiled: January 17, 2006Date of Patent: February 12, 2008Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Robert E. Campbell, Geoffrey S. Baird
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Patent number: 7173130Abstract: Methods and compositions are provided for detecting changes in membrane potential in membranes biological systems. In one aspect, the method comprises; a) providing a living cell with a first reagent comprising a charged hydrophobic molecule which is typically a fluorescence resonance energy transfer (FRET) acceptor or donor, or is a quencher and is capable of redistributing within the membrane of a biological membrane in response to changes in the potential across the membrane; b) providing the cell with a second reagent that can label the first face or the second face of a biological membrane within the cell; c) detecting light emission from the first reagent or the second reagent. One aspect of this method involves monitoring membrane potential changes in subcellular organelle membranes in a living cells. Another aspect of the invention is the use of certain embodiments of the method for the screening of test chemicals for activity to modulate the activity of a target ion channel.Type: GrantFiled: September 28, 2001Date of Patent: February 6, 2007Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Jesus E. Gonzalez, III
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Patent number: 7160732Abstract: The present invention is directed, in part, to fluorescein-based ligands for detection of metal ions, and methods of making and using the same.Type: GrantFiled: July 9, 2001Date of Patent: January 9, 2007Assignee: Massachusetts Institute of TechnologyInventors: Stephen J. Lippard, Shawn Burdette, Scott Hilderbrand, Roger Y. Tsien, Grant K. Walkup
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Patent number: 7157566Abstract: The present invention relates generally to variant fluorescent proteins, and more specifically to monomeric and dimeric forms of Anthozoan fluorescent proteins. In one aspect, the present invention provides variants of fluorescent proteins, where the variants have a reduced propensity to tetramerize, and form dimeric or monomeric structures. The invention also relates to methods of making and using such fluorescent protein monomers and dimers.Type: GrantFiled: April 10, 2002Date of Patent: January 2, 2007Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Robert E. Campbell
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Patent number: 7157575Abstract: Substrates for ?-lactamase of the general formula I in which one of X and Y is a fluorescent donor moiety and the other is a quencher (which may or may not re-emit); R? is selected from the group consisting of H, lower (i.e., alkyl of 1 to about 5 carbon atoms) and (CH2)nOH, in which n is 0 or an integer from 1 to 5; R? is selected from the group consisting of H, physiologically acceptable metal and ammonium cations, —CHR2OCO(CH2)nCH3, —CHR2OCOC(CH3)3, acylthiomethyl, acyloxy-alpha-benzyl, delta-butyrolactonyl, methoxycarbonyloxymethyl, phenyl, methylsulphinylmethyl, beta-morpholinoethyl, dialkylaminoethyl, acyloxyalkyl, dialkylaminocarbonyloxymethyl and aliphatic, in which R2 is selected from the group consisting of H and lower alkyl; A is selected from the group consisting of S, O, SO, SO2 and CH2; and Z? and Z? are linkers for the fluorescent donor and quencher moieties.Type: GrantFiled: October 24, 2002Date of Patent: January 2, 2007Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Gregor Zlokarnik
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Patent number: 7142290Abstract: The invention provides for a detector assembly, fiber assembly and screening system for optical measurements.Type: GrantFiled: February 15, 2006Date of Patent: November 28, 2006Assignee: Aurora Discovery, Inc.Inventors: Roger Y. Tsien, Peter J. Coassin, Andrew A. Pham, Alec Tate Harootunian, Minh Vuong
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Patent number: 7138503Abstract: The present invention features biarsenical molecules. Target sequences that specifically react with the biarsenical molecules are also included. The present invention also features kits that include biarsenical molecules and target sequences. Tetraarsenical molecules are also featured in the invention.Type: GrantFiled: February 3, 2004Date of Patent: November 21, 2006Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, B. Albert Griffin
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Patent number: 7118899Abstract: Methods and compositions are provided for detecting changes in membrane potential in membranes biological systems. In one aspect, the method comprises; a) providing a living cell with a first reagent comprising a charged hydrophobic molecule which is typically a fluorescence resonance energy transfer (FRET) acceptor or donor, or is a quencher and is capable of redistributing within the membrane of a biological membrane in response to changes in the potential across the membrane; b) providing the cell with a second reagent that can label the first face or the second face of a biological membrane within the cell; c) detecting light emission from the first reagent or the second reagent. One aspect of this method involves monitoring membrane potential changes in subcellular organelle membranes in a living cells. Another aspect of the invention is the use of certain embodiments of the method for the screening of test chemicals for activity to modulate the activity of a target ion channel.Type: GrantFiled: December 31, 2002Date of Patent: October 10, 2006Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Jesus E. Gonzalez, III
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Patent number: 7115401Abstract: Methods and compositions are provided for determining the potential of a membrane. In one aspect, the method comprises: (a) introducing a first reagent comprising a hydrophobic fluorescent ion capable of redistributing from a first face of the membrane to a second face of the membrane in response to changes in the potential of the membrane, as described by the Nernst equation, (b) introducing a second reagent which labels the first face or the second face of the membrane, which second reagent comprises a chromophore capable of undergoing energy transfer by either (i) donating excited state energy to the fluorescent ion, or (ii) accepting excited state energy from the fluorescent ion, (c) exposing the membrane to radiation; (d) measuring energy transfer between the fluorescent ion and the second reagent, and (e) relating the energy transfer to the membrane potential. Energy transfer is typically measured by fluorescence resonance energy transfer.Type: GrantFiled: December 31, 2002Date of Patent: October 3, 2006Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Jesus E. Gonzalez, III
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Patent number: 7087416Abstract: Methods and compositions are provided for detecting changes in membrane potential in membranes biological systems. In one aspect, the method comprises; a) providing a living cell with a first reagent comprising a charged hydrophobic molecule which is typically a fluorescence resonance energy transfer (FRET) acceptor or donor, or is a quencher and is capable of redistributing within the membrane of a biological membrane in response to changes in the potential across the membrane; b) providing the cell with a second reagent that can label the first face or the second face of a biological membrane within the cell; c) detecting light emission from the first reagent or the second reagent. One aspect of this method involves monitoring membrane potential changes in subcellular organelle membranes in a living cells. Another aspect of the invention is the use of certain embodiments of the method for the screening of test chemicals for activity to modulate the activity of a target ion channel.Type: GrantFiled: December 31, 2002Date of Patent: August 8, 2006Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Jesus E. Gonzalez, III
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Patent number: 7067324Abstract: The present invention provides a method for reducing undesirable light emission from a sample using at least one photon producing agent and at least one photon reducing agent (e.g. dye-based photon reducing agents). The present invention further provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one collisional quencher. The present invention also provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one quencher, such as an electronic quencher. The present invention also provides a system and method of screening test chemicals in fluorescent assays using photon reducing agents. The present invention also provides compositions, pharmaceutical compositions, and kits for practicing these methods.Type: GrantFiled: January 12, 2001Date of Patent: June 27, 2006Assignee: Invitrogen CorporationInventors: Tom Knapp, Gregor Zlokarnik, Paul Negulescu, Roger Y. Tsien, Tim Rink
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Patent number: 7060869Abstract: Fluorescent indicators including a binding protein moiety, a donor fluorescent protein moiety, and an acceptor fluorescent protein moiety are described. The binding protein moiety has an analyte-binding region which binds an analyte and causes the indicator to change conformation upon exposure to the analyte. The donor moiety and the acceptor moiety change position relative to each other when the analyte binds to the analyte-binding region. The donor moiety and the acceptor moiety exhibit fluorescence resonance energy transfer when the donor moiety is excited and the distance between the donor moiety and the acceptor moiety is small. The indicators can be used to measure analyte concentrations in samples, such as calcium ion concentrations in cells.Type: GrantFiled: April 20, 2000Date of Patent: June 13, 2006Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Atsushi Miyawaki
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Patent number: 7060793Abstract: Polynucleotides encoding fluorescent indicators, which contain a sensor polypeptide inserted within a fluorescent moiety, are provided, as are polypeptides encoded by such polynucleotides. Also provided are circularly permuted fluorescent polypeptides and polynucleotides encoding the circularly permuted fluorescent polypeptides. In addition, methods of using the fluorescent indicators and the circularly permuted fluorescent polypeptides are provided.Type: GrantFiled: October 23, 2001Date of Patent: June 13, 2006Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Geoffrey Baird
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Patent number: 7041821Abstract: The invention provides Zn-chelating compounds that are molecularly engineered to bind to a specific target sequence in a protein of interest. The Zn2+ ion is far less toxic and promiscuous than nickel and therefore provides an attractive alternative to Ni-based labeling systems. Invention Zn-chelating compounds also do not require oxidizable thiols and therefore can be used in non-reducing environments such as the surface of living cells. In addition, the target sequence is genetically encodable and requires incorporation of only a few amino acids, unlike fusions to fluorescent proteins such as GFP.Type: GrantFiled: January 16, 2004Date of Patent: May 9, 2006Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, Christina Hauser
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Patent number: 7022826Abstract: A non-oligomerizing fluorescent protein, which is derived from a fluorescent protein having at least one mutation that reduces or eliminates the ability of the fluorescent protein to oligomerize, is provided. The non-oligomerizing fluorescent protein can be derived from a naturally occurring green fluorescent protein, a red fluorescent protein, or other fluorescent protein, or a fluorescent protein related thereto. Also provided is a fusion protein, which includes a non-oligomerizing fluorescent protein linked to at least one polypeptide of interest. In addition, a polynucleotide encoding a non-oligomerizing fluorescent protein is provided, as is a recombinant nucleic acid molecule, which includes polynucleotide encoding a non-oligomerizing fluorescent protein operatively linked to at least a second polynucleotide.Type: GrantFiled: February 26, 2001Date of Patent: April 4, 2006Assignee: The Regents of the University of CaliforniaInventors: Roger Y. Tsien, David A. Zacharias, Geoffrey S. Baird