Producing Labeled Antigens Patents (Class 436/544)
  • Patent number: 8501498
    Abstract: This invention pertains to methods, mixtures, kits and/or compositions for the determination of analytes by mass analysis using unique labeling reagents or sets of unique labeling reagents. The labeling reagents can be isomeric or isobaric and can be used to produce mixtures suitable for multiplex analysis of the labeled analytes.
    Type: Grant
    Filed: November 13, 2009
    Date of Patent: August 6, 2013
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: Xiongwei Yan, Pau-Miau Yuan, Sylvia W. Yuen, Kuo-Liang Hsi, Joe Y. Lam, Krishna G. Upadhya, Subhakar Dey, Darryl J. C. Pappin, Sasi Pillai, Helena Huang, Subhasish Purkayastha
  • Patent number: 8486401
    Abstract: Monoclonal antibodies, synthetic and biotechnological derivatives thereof (ScFv or others) are able to recognise the NGF high affinity receptor, TrkA, and act as NGF-antagonist molecules. Pharmacological compositions for therapy, gene therapy, diagnostics of neurological pathologies are also described. Transgenic animal models to study such pathologies are also described.
    Type: Grant
    Filed: September 11, 2009
    Date of Patent: July 16, 2013
    Assignee: Lay Line Genomics S.p.A.
    Inventor: Michal M. Novak
  • Patent number: 8460877
    Abstract: The present invention relates to a technique of measuring a protein based on a degree of coloring in a liquid sample mixed with a protein measurement indicator. In the present invention, information reflecting creatinine concentration in the liquid sample is obtained, and then an influence quantity caused by creatinine to the protein concentration measurement is eliminated based on the information.
    Type: Grant
    Filed: January 21, 2005
    Date of Patent: June 11, 2013
    Assignee: Arkray, Inc.
    Inventors: Hideko Kosaka, Hisashi Sakamoto
  • Patent number: 8409821
    Abstract: A method of assessing arachidonic acid (AA) metabolites-dependent hypertension by measuring glucuronidated dihydroxyeicosatrienoic acids (DHETs) and DHET metabolites in a biological sample which contains the epitopes unique to DHET (using any methods including GC/MS, LC/MS or ELISA). An example of the glucuronidated DHET metabolite is DHET-alcohols such as omega or omega-1 oxidated DHET and DHET esterified glycerol. The method further includes determining the amount of glucuronidated molecules containing a DHET-specific epitope which is immunoreactive with antibodies produced against DHETs.
    Type: Grant
    Filed: March 3, 2010
    Date of Patent: April 2, 2013
    Assignee: Detroit R&D
    Inventors: Hyesook Kim, Jorge H. Capdevila, Raymond F. Novak, Deanna Kroetz
  • Patent number: 8383425
    Abstract: The invention provides methods and compositions for the rapid and sensitive detection of post-translationally modified proteins, and particularly of those with post-translational glycosylations. The methods can be used to detect O-GlcNAc posttranslational modifications on proteins on which such modifications were undetectable using other techniques. In one embodiment, the method exploits the ability of an engineered mutant of ?-1,4-galactosyltransferase to selectively transfer an unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once transferred, the ketone moiety serves as a versatile handle for the attachment of biotin, thereby enabling detection of the modified protein. The approach permits the rapid visualization of proteins that are at the limits of detection using traditional methods. Further, the preferred embodiments can be used for detection of certain disease states, such as cancer, Alzheimer's disease, neurodegeneration, cardiovascular disease, and diabetes.
    Type: Grant
    Filed: October 21, 2010
    Date of Patent: February 26, 2013
    Assignee: California Institute of Technology
    Inventors: Linda Hsieh-Wilson, Nelly Khidekel, Hwan-Ching Tai, Sabine Arndt
  • Patent number: 8357793
    Abstract: This invention provides for labeling reagents, labeled targets and processes for preparing labeling reagents. The labeling reagents can take the form of cyanine dyes, xanthene dyes, porphyrin dyes, coumarin dyes or composite dyes. These labeling reagents are useful for labeling probes or targets, including nucleic acids and proteins. These reagents can be usefully applied to protein and nucleic acid probe based assays. They are also applicable to real-time detection processes.
    Type: Grant
    Filed: January 22, 2004
    Date of Patent: January 22, 2013
    Assignee: Enzo Life Sciences, Inc.
    Inventors: Jannis G. Stavrianopoulos, Flazar Rabbani
  • Patent number: 8344115
    Abstract: This invention pertains to a method for detecting a compound in the presence of other compounds that are substantially similar in structure and metabolically related to the analyte. The invention is particularly suited for the detection of S-adenosylmethionine in the presence of S-adenosylhomocysteine, other nucleosides and derivatives in a biological sample. The methods of this invention involve an antibody produced specifically against S-adenosylmethionine; particularly, analogs modified strategically at the sulfonium position. An assay protocol comprises chemically modified analyte analog linked to an enzymatic reporter and the aforementioned antibody was used to demonstrate the assay specificity and sensitivity. Additional assay method with immobilized immunogen, the specific antibody, and an enzyme labeled secondary antibody was also described for illustration. The invention also features hapten design and novel compounds used as haptens to prepare immunogen and for the specific antibody production.
    Type: Grant
    Filed: April 17, 2009
    Date of Patent: January 1, 2013
    Inventors: Chiu Chin Chang, Chan-Sui Pang, legal representative
  • Patent number: 8309695
    Abstract: The present invention relates to a labeling reagent of formula: in which: R1 represents at least one detectable label, L and A are each a linker arm, n is an integer equal to 1, and u is an integer between 0 and 2. The present invention also describes a method of synthesizing said markers and also applications for the labeling of biological molecules, more particularly nucleic acids, with a labeling reagent bearing diazo and nitro functions. The invention is particularly suitable for use in the diagnostics field.
    Type: Grant
    Filed: June 9, 2008
    Date of Patent: November 13, 2012
    Assignees: Biomerieux, CNRS, Universite de Strasbourg
    Inventors: Alain Laurent, Ali Laayoun, Mitsuharu Kotera
  • Patent number: 8278120
    Abstract: The present invention provides: a method of changing the fluorescence wavelength of a GFP-like fluorescent protein from copepod while maintaining recombinant expression efficiency, which comprises identifying a structural factor for determining the fluorescence wavelength thereof in the three-dimensional structure of the protein and modifying amino acid residues associated with the structural factor; and a modified fluorescent protein obtained by applying said method. For example, with regard to a GFP-like fluorescent protein from Chiridius poppei, His52 in an ? helix-like secondary structure: PFLLSHCMGYGFYHF (?1 47-61) comprising a fluorescent moiety site GYG is replaced with an aromatic amino acid selected from Phe, Tyr and Trp, so as to cause a red shift of the fluorescent peak wavelength; or it is replaced with Ala, Val, Ile, Leu, Gly, Cys, Met, Ser, Thr, or Asp, Asn, Glu or Gln, so as to cause a blue shift of the fluorescence peak wavelength.
    Type: Grant
    Filed: January 25, 2007
    Date of Patent: October 2, 2012
    Assignee: NEC Soft, Ltd.
    Inventors: Kyoko Suto, Hiromi Takenaka, Yasuhiro Takenaka
  • Patent number: 8247180
    Abstract: The invention provides methods and kits for detecting and/or measuring receptor homodimers on a cell surface membrane. In one aspect, the methods employ pairs of probes comprising binding compounds and a cleaving probe, such that at least one binding compound binds specifically to the same epitope of a membrane-bound analyte as the cleaving probe. The binding compound includes one or more molecular tags attached through a cleavable linkage, and the cleaving probe includes a cleavage-inducing moiety that can cleave the linkage when within a defined proximity thereto. Binding of the two probes to a homodimer of a cell surface molecules results in release of molecular tags from the binding compounds, providing a measure of formation of the homodimeric complex.
    Type: Grant
    Filed: July 18, 2008
    Date of Patent: August 21, 2012
    Assignee: Monogram Biosciences, Inc.
    Inventors: Sailaja Pidaparthi, Yining Shi, Rajiv Dua, Po-Ying Chan-Hui, Sharat Singh
  • Patent number: 8198031
    Abstract: Methods are provided for detecting the formation of complexes of molecules, especially proteins, in a sample, such as a cell or tissue lysate. In one aspect, a cleaving probe specific for a first protein in a complex and one or more binding compounds specific for one or more second proteins in a complex are provided. Upon binding, the cleaving probe is induced to generate an active species, such as singlet oxygen, that cleaves molecular tags attached to the binding compounds only in the local region of the cleaving probe. The released molecular tags are separated from the assay mixture and from one another to provide a readout that is related to the number and types of proteins present in the complex.
    Type: Grant
    Filed: March 12, 2007
    Date of Patent: June 12, 2012
    Assignee: Monogram Biosciences, Inc.
    Inventors: Po-Ying Chan-Yui, Sharat Singh, Hossein Salimi-Moosavi, Yining Shi, Sailaja Pidaparthi, Rajiv Dua, Ali Mukherjee
  • Patent number: 8198101
    Abstract: A bifunctional polyazamacrocyclic chelating agent of the formula (I): wherein: and the variables A, L, Q, Q1, X, Y, Z, Z1, m, n and r are as defined in the description of the present application. Also described is a complex of the above chelating agent to an ion of a metal ion, such as an ion of 90Y, 111Li or 177Lu; a conjugate of the complex covalently attached to a biological carrier; and a pharmaceutical composition containing the conjugate. A method of therapeutic treatment of a mammal involving administration of the pharmaceutical composition is also described.
    Type: Grant
    Filed: March 6, 2007
    Date of Patent: June 12, 2012
    Assignee: Nordion (Canada) Inc.
    Inventors: Zoltan Kovacs, Garry E. Kiefer, Corinne Bensimon, A. Dean Sherry, Gyula Tircso
  • Patent number: 8163562
    Abstract: 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: Grant
    Filed: August 23, 2010
    Date of Patent: April 24, 2012
    Assignee: Life Technologies Corporation
    Inventors: Tom Knapp, Gregory Zlokarnik, Paul Negulescu, Roger Tsien, Timothy Rink
  • Patent number: 8133743
    Abstract: Phenobarbital derivatives synthesized out of the alkyl chain at the 5-position, particularly with hydrophilic properties, and carrying an active ester at the end, allow formation of aminodextran conjugates that give curves in the desired range of the assay in the ONLINE TDM microparticle assay format when matched against the Roche FPIA antibody specific for phenobarbital (“an antibody specific for phenobarbital”).
    Type: Grant
    Filed: September 23, 2008
    Date of Patent: March 13, 2012
    Assignee: Roche Diagnostics Operations, Inc.
    Inventor: Raymond Hui
  • Patent number: 8133694
    Abstract: The preparation of vitamin D compounds of formula (I) with a label attached to a spacer group in the 3 position is disclosed. In the above formula (I), O represents the oxygen atom of an ether group; Y represents hydrogen or hydroxy; A represents a label such as biotin, digoxigenin, or another vitamin D group; R represents a substituted hydrocarbon side-group of vitamin D or a vitamin D metabolite. Also disclosed is a method of measuring 25-hydroxy vitamin D metabolite and a 1?,25-dihydroxy vitamin D metabolite in a sample.
    Type: Grant
    Filed: March 3, 2004
    Date of Patent: March 13, 2012
    Assignees: Immundiagnostik AG, Biomedica GmbH
    Inventors: Franz Paul Armbruster, Wolfgang Voelter, Jens Tampe, Christian Birkmayer
  • Patent number: 8133695
    Abstract: Disclosed are assays, methods, and kits for the screening of test compounds for their capability to induce cardiotoxicity in a subject. In particular, whether a test compound has the effect to prolong the Q-T interval as measured by an electrocardiogram in a human. The assays, methods, and kits disclosed herein make use of the binding interaction between novel fluorescent tracers and the hERG K+ channel, and the propensity of a test compound to influence that binding interaction.
    Type: Grant
    Filed: February 27, 2009
    Date of Patent: March 13, 2012
    Assignee: Life Technologies Corporation
    Inventors: David Piper, Kurt Vogel, Mohammed Saleh Shekhani, Stephen Hess, Steve Duff, Thomas Livelli, Zhong Zhong
  • Patent number: 8129505
    Abstract: The present invention provides a process for producing a comb polymer comprising the steps of: a) providing: (i) (w+z) molar equivalents of a monomer; (ii) one molar equivalent of an initiator compound of formula (IX), wherein B3 represents a halogen, B2 represents H or a halogen, Y1 represents a group capable of attaching the residue of an antibody or fragment thereof or capable of being converted into such a group, L represents a linker group, y is 1, 2 or 3, w is at least 1 and z is 0 or greater; (iii) a catalyst capable of catalysing the polymerization of a plurality of the monomers to produce the comb polymer; and b) causing the catalyst to catalyse, in combination with the initiator, the polymerization of a plurality of the monomers (i) to produce the comb polymer.
    Type: Grant
    Filed: September 12, 2006
    Date of Patent: March 6, 2012
    Assignee: UCB Pharma S.A.
    Inventors: Timothy John Norman, Benjamin Charles De Candole, Mezher Hussein Ali
  • Patent number: 8124364
    Abstract: A method for the conditioning of an extracorporeal device is described, as well as method for extracorporeal extraction of toxic material from mammalian body fluids in connection with diagnosis or treatment of a mammalian condition or disease, in which methods reagents having the ability to extract toxic material from mammalian body fluids are involved, and an extracorporeal device comprising said reagent.
    Type: Grant
    Filed: June 18, 2001
    Date of Patent: February 28, 2012
    Assignee: Glycorex Transplantation AB
    Inventors: Bengt Sandberg, Scott Wilbur, Rune Nilsson
  • Patent number: 8075891
    Abstract: The invention relates to an epitope protection assay for use in diagnosis, prognosis and therapeutic intervention in diseases, for example, involving polypeptide aggregation, such as prion infections. The methods of the invention first block accessible polypeptide target epitope with a blocking agent. After denaturation of the polypeptide, a detecting agent is used to detect protein with target epitope that was inaccessible during contact with the blocking agent. The invention also relates to novel amyotrophic lateral sclerosis-specific epitopes and their uses to make antibodies, and to the novel antibodies and uses thereof.
    Type: Grant
    Filed: June 2, 2010
    Date of Patent: December 13, 2011
    Assignee: Amorfix Life Sciences Ltd.
    Inventor: Neil Cashman
  • Patent number: 8067247
    Abstract: The invention relates to the use a BD16 and/or BB18 anti-CD100 antibody or of a chimeric or humanized or human form thereof, or a fragment thereof, for the therapy or diagnosis of a central nervous system disorder, more particularly a myelin disorder or a disease that affects oligodendrocytes, such as multiple sclerosis or HTLV-1 associated myelopathy or peripheral myelinating cells.
    Type: Grant
    Filed: February 2, 2004
    Date of Patent: November 29, 2011
    Assignee: Institut National de la Sante Et de la Recherche Medicale (INSERM)
    Inventors: Marie-Françoise Belin, Pascale Giraudon, Laurence Boumsell, Armand Bensussan
  • Patent number: 8048637
    Abstract: A diagnostic composition to detect antibodies in a sample obtained from an animal or human being infected by Trichinella, comprising at least one peptide containing a series of amino acids that form a continuous or discontinuous epitope recognized by sera from pigs infected with Trichinella.
    Type: Grant
    Filed: June 29, 2007
    Date of Patent: November 1, 2011
    Assignee: Prionics AG
    Inventors: Patrik Buholzer, Alex Raber, Paul Price, Daniel Zwald, Weldy Bonilla Pinschewer, Roger Marti, Jurg Weidmann, Christoph Stamm
  • Patent number: 8039273
    Abstract: Ligand Drug conjugate compounds comprising a ?-glucuronide-based linker and methods of using such compounds are provided.
    Type: Grant
    Filed: July 18, 2006
    Date of Patent: October 18, 2011
    Assignee: Seattle Genetics, Inc.
    Inventor: Scott Jeffrey
  • Patent number: 8034636
    Abstract: In accordance with the present invention, it has been discovered that introduction of hydrophilic sulfoalkyl substituents and/or hydrophilic linkers derived from homocysteic acid, cysteic acid, glycine peptides, tetraethylene oxide, and the like, offset the hydrophobicity of the acridinium ring system to produce a more soluble label which can be attached to an antibody at higher loading before precipitation and aggregation problems are encountered. Additional compounds described herein contain linkers derived from short peptides and tetraethylene oxide which increase aqueous solubility due to hydrogen bonding with water molecules. The present invention also embraces reagents for multiple acridinium labeling for signal amplification composed of a peptide bearing several acridinium esters with sulfonate groups at regularly spaced intervals for increased solubility. The invention also embraces assays employing the above-described compounds.
    Type: Grant
    Filed: September 23, 2010
    Date of Patent: October 11, 2011
    Assignee: Quest Diagnostics Investments Incorporated
    Inventors: Ramon Evangelista, Martha Garrity
  • Patent number: 8026109
    Abstract: Novel hapten-carrier conjugates are capable of inducing the production of antibodies, in vivo, that specifically bind to nicotine. These conjugates comprise a nicotine hapten conjugated to an immunogenic carrier protein. The novel conjugates preserve the chirality of nicotine in its native (S)-(?) state, and have good stability properties. The conjugates are useful in formulating vaccines for active immunization, that are used to prevent and treat nicotine addiction. The antibodies raised in response to the nicotine hapten-carrier conjugate are used for passive immunization. These antibodies are administered for prevention and treatment of nicotine addiction.
    Type: Grant
    Filed: July 14, 2010
    Date of Patent: September 27, 2011
    Assignee: Nabi Biopharmaceuticals, Inc.
    Inventors: Sofiane Ennifar, Ali Ibrahim Fattom, Robert B. Naso
  • Patent number: 7964415
    Abstract: Water soluble, polyethylenimine polymers, conjugated to one or more active moiety are taught. Also taught are methods of making same, kits comprising same, and use of same in immunoassay systems.
    Type: Grant
    Filed: April 26, 2006
    Date of Patent: June 21, 2011
    Assignee: CardioGenics Inc.
    Inventors: Pavel Zhelev, Amer Alagic, Yahia A. Gawad
  • Patent number: 7947513
    Abstract: This invention pertains to methods, kits and/or compositions for the determination of analytes by mass analysis using unique labeling reagents or sets of unique labeling reagents. The labeling reagents can be isomeric or isobaric and can be used to produce mixtures suitable for multiplex analysis of the labeled analytes.
    Type: Grant
    Filed: February 12, 2007
    Date of Patent: May 24, 2011
    Assignee: DH Technologies Ptd. Ltd.
    Inventors: Darryl J. C. Pappin, Michael Bartlett-Jones
  • Patent number: 7939267
    Abstract: Methods, compositions and kits are provided for assessing angiogenesis through sensitive, direct detection of activation of endothelial cells at molecular levels. In general, activation of endothelial cells is detected by measuring the levels of cellular components and their protein complexes participating in a specific angiogenesis signaling pathway in endothelial cells. The methods can be used for assessing status of diseases associated with undesirable angiogenesis, such as the likelihood of developing the disease, presence or absence of the disease, prognosis of the disease and the likelihood of response or resistance to a particular anti-angiogenic therapy. The methods can also be used to guide the design of effective therapeutic regimens targeting a specific angiogenic signaling pathway, as well as in conjunction with therapeutic intervention of diseases or conditions associated with undesirable angiogenesis.
    Type: Grant
    Filed: November 3, 2005
    Date of Patent: May 10, 2011
    Assignee: Laboratory Corporation of America Holdings
    Inventors: Sean C. Moore, Sharat Singh, Hossein Salimi-Moosavi, Liching Cao, Jeff Sperinde
  • Patent number: 7906629
    Abstract: Activated haptens useful for generating immunogens to HIV protease inhibitors, immunogens useful for producing antibodies to HIV protease inhibitors, and antibodies and labeled conjugates useful in immunoassays for the HIV protease inhibitor saquinavir. The novel haptens feature an activated functionality at the central, non-terminal hydroxyl group. Also described are monoclonal antibodies specific for saquinavir having less than 10% cross-reactivity with lopinavir, nelfinavir, amprenavir, ritonavir, and indinavir, and a murine hybridoma producing said antibodies.
    Type: Grant
    Filed: January 31, 2007
    Date of Patent: March 15, 2011
    Assignee: Roche Diagnostics Operations, Inc.
    Inventors: Gerald F. Sigler, Raymond A. Hui, Ina Deras, Erasmus Huber, Herbert W. Von Der Eltz
  • Patent number: 7901893
    Abstract: The present invention provides human, rat and mouse NPCIL1 polypeptides and polynucleotides encoding the polypeptides. Methods for detecting ligands which bind to NPC1L1 and block intestinal cholesterol absorption are provided. Also included is a method of identifying ligands which bind to NPCILI using membranes derived from brush border membrane preparations. Compounds that bind to NPCILI can be used for inhibiting intestinal cholesterol absorption in a subject.
    Type: Grant
    Filed: January 14, 2005
    Date of Patent: March 8, 2011
    Assignee: Merck Sharp & Dohme Corp.
    Inventor: Maria Margarita Garcia-Calvo
  • Patent number: 7897404
    Abstract: The invention relates to a process for the production of a biomolecule-linker conjugate of uniform stochiometry. It especially relates to a conjugate consisting of a biomolecule of a molecular weight between 5 kD and 500 kD and a hydrophilic linker molecule said linker having a molecular weight between 1 and 15 kD and between 4 and 60 charged residues, characterized in that said conjugate comprises at least one biomolecule-linker product of uniform stoichiometry in a pre-selected amount.
    Type: Grant
    Filed: August 26, 2001
    Date of Patent: March 1, 2011
    Assignee: Roche Diagnostics Operations, Inc.
    Inventors: Eva Hoess, Herbert Andres, Frederic Donie, Rudolf Vogel, Hans-Peter Josel, Rupert Hermann, Herbert Von Der Eltz
  • Patent number: 7893220
    Abstract: Novel conjugates of busulfan and novel busulfan immunogens derived from ?-substituted derivatives of busulfan and antibodies generated by these busulfan linked immunogens are useful in immunoassays for the quantification and monitoring of busulfan in biological fluids.
    Type: Grant
    Filed: July 9, 2008
    Date of Patent: February 22, 2011
    Assignee: Saladax Biomedical Inc.
    Inventors: Salvatore J. Salamone, Jodi Blake Courtney, Shu He
  • Patent number: 7888055
    Abstract: A substrate comprises a surface, and a plurality of moieties, on at least a portion of the surface. The moieties are moieties of formula: Surf-L-Q-T, where -T comprises a reactant ligand, and Surf- designates where the moiety attaches to the surface. The substrate can be made into a protein chip by the reaction of a reactant ligand and a fusion polypeptide, where the fusion polypeptide includes a capture polypeptide moiety which corresponds to the reactant ligand.
    Type: Grant
    Filed: December 21, 2006
    Date of Patent: February 15, 2011
    Assignee: The University of Chicago
    Inventors: Milan Mrksich, Christian Hodneland
  • Patent number: 7842517
    Abstract: The invention provides methods and compositions for the rapid and sensitive detection of post-translationally modified proteins, and particularly of those with post-translational glycosylations. The methods can be used to detect O-GlcNAc posttranslational modifications on proteins on which such modifications were undetectable using other techniques. In one embodiment, the method exploits the ability of an engineered mutant of ?-1,4-galactosyltransferase to selectively transfer an unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once transferred, the ketone moiety serves as a versatile handle for the attachment of biotin, thereby enabling detection of the modified protein. The approach permits the rapid visualization of proteins that are at the limits of detection using traditional methods. Further, the preferred embodiments can be used for detection of certain disease states, such as cancer, Alzheimer's disease, neurodegeneration, cardiovascular disease, and diabetes.
    Type: Grant
    Filed: June 15, 2007
    Date of Patent: November 30, 2010
    Assignee: California Institute of Technology
    Inventors: Linda Hseih-Wilson, Nelly Khidekel, Hwan-Ching Tai, Sabine Arndt
  • Patent number: 7824928
    Abstract: In accordance with the present invention, it has been discovered that introduction of hydrophilic sulfoalkyl substituents and/or hydrophilic linkers derived from homocysteic acid, cysteic acid, glycine peptides, tetraethylene oxide, and the like, offset the hydrophobicity of the acridinium ring system to produce a more soluble label which can be attached to an antibody at higher loading before precipitation and aggregation problems are encountered. Additional compounds described herein contain linkers derived from short peptides and tetraethylene oxide which increase aqueous solubility due to hydrogen bonding with water molecules. The present invention also embraces reagents for multiple acridinium labeling for signal amplification composed of a peptide bearing several acridinium esters with sulfonate groups at regularly spaced intervals for increased solubility. The invention also embraces assays employing the above-described compounds.
    Type: Grant
    Filed: November 7, 2007
    Date of Patent: November 2, 2010
    Assignee: Quest Diagnostics Investments Incorporated
    Inventors: Ramon Evangelista, Martha Garrity
  • Patent number: 7811828
    Abstract: Described is a method for identifying and quantifying of tumour-associated peptides, wherein first at least two different sources for obtaining the peptide are provided (tumourous and healthy tissue), and, separately of one another, the peptides from the different sources are chemically modified in an identical manner by using at least two different stable isotopes of the same element. Subsequently, the peptides are isolated by a chromatographic method, and the amino acid sequences of the peptides are determined, wherein the determination of the relative amount ratios of peptides having the identical sequence from different samples one to the other occurs by using a stable isotope in the chemical modification. Furthermore, the invention relates to a tumour-associated peptide having an amino acid sequence that is selected from the group consisting of SEQ-ID No.
    Type: Grant
    Filed: January 28, 2005
    Date of Patent: October 12, 2010
    Assignee: Immatics Biotechnologies GmbH
    Inventors: Claudia Lemmel, Hans-Georg Rammensee
  • Patent number: 7776620
    Abstract: Novel hapten-carrier conjugates are capable of inducing the production of antibodies, in vivo, that specifically bind to nicotine. These conjugates comprise a nicotine hapten conjugated to an immunogenic carrier protein. The novel conjugates preserve the chirality of nicotine in its native (S)-(?) state, and have good stability properties. The conjugates are useful in formulating vaccines for active immunization, that are used to prevent and treat nicotine addiction. The antibodies raised in response to the nicotine hapten-carrier conjugate are used for passive immunization. These antibodies are administered for prevention and treatment of nicotine addiction.
    Type: Grant
    Filed: July 20, 2007
    Date of Patent: August 17, 2010
    Assignee: Nabi Biopharmaceuticals
    Inventors: Sofiane Ennifar, Ali Ibrahim Fattom, Robert B. Naso
  • Patent number: 7736846
    Abstract: The present invention relates to regulation of inflammation. More particularly, the present invention is directed to nucleic acids encoding components of the ubiquitin ligation pathway, e.g., ubiquitin and ubiquitin-like molecules, E1, E2, and E3 proteins and their substrates, which are involved in modulation of the inflammatory process. The invention further relates to methods for identifying and using agents, including small molecule chemical compositions, antibodies, peptides, cyclic peptides, nucleic acids, RNAi, antisense nucleic acids, and ribozymes, that modulate the inflammatory process via modulation of the ubiquitin ligation pathway; as well as to the use of expression profiles and compositions in diagnosis and therapy related to regulation of inflammation and modulation of cytokine signaling involved in inflammation, e.g., for treatment of infection, autoimmune disease and other diseases related to the inflammatory process.
    Type: Grant
    Filed: August 28, 2003
    Date of Patent: June 15, 2010
    Assignee: Rigel Pharmaceuticals, Inc.
    Inventors: Esteban Masuda, Brian Wong
  • Patent number: 7732160
    Abstract: Compounds of methamphetamine derivatives having a meta-substituted alkyl linker on the benzene ring and a protective group on the nitrogen of the methamphetamine hapten. Such compounds have the structure. wherein R1 is an alkyl linker comprising 2-15 carbon atoms and 0-6 heteroatoms, R2 is a leaving group, and R3 is a protecting group.
    Type: Grant
    Filed: October 1, 2007
    Date of Patent: June 8, 2010
    Assignee: Roche Diagnostics Operations, Inc.
    Inventors: Raymond A. Hui, Stephen S. Vitone
  • Patent number: 7695927
    Abstract: A method to assess arachidonic acid (AA) metabolites-dependent hypertension by measuring glucuronidated dihydroxyeicosatrienoic acids (DHETs) and DHET metabolites in a biological sample which contains the epitopes unique to DHET (using any methods including GC/MS, LC/MS or ELISA) is disclosed. An example of the glucuronidated DHET metabolite is DHET-alcohols such as omega or omega-1 oxidated DHET and DHET esterified glycerol. The method further includes determining the amount of glucuronidated molecules containing a DHET-specific epitope which is immunoreactive with antibodies produced against DHETs. The present invention measuring glucuronidated DHET levels in a biological sample is useful for drug development and monitoring efficiency of drug treatment of a mammal who has AA epoxygenase-, epoxide hydrolase-and/or UDP-glucuronosyl transferase-dependent hypertension.
    Type: Grant
    Filed: March 17, 2006
    Date of Patent: April 13, 2010
    Assignee: Detroit R & D
    Inventors: Hyesook Kim, Jorge H. Capdevila, Raymond R. Novak, Deanna Kroetz
  • Patent number: 7695980
    Abstract: The present invention relates to novel chemiluminescent compounds, to a method for synthesizing these compounds, to derivatives and conjugates comprising these compounds, to the use of these compounds or conjugates thereof in chemiluminescence based assays, especially in immunoassays.
    Type: Grant
    Filed: January 25, 2006
    Date of Patent: April 13, 2010
    Assignee: Roche Diagnostics Operations, Inc.
    Inventors: Dieter Heindl, Rupert Herrmann, Wolfgang Jenni, Heribert Maerz
  • Patent number: 7691635
    Abstract: The present invention relates to a temperature-stable labeling reagent of formula (0): in which: R1 represents H or an alkyl, aryl or substituted aryl group, R2 represents a detectable marker or at least two detectable markers interlinked by at least one multimeric structure, L is a linker arm comprising a linear chain of at least two covalent bonds and n is an integer equal to 0 or 1, R3 and R4 represent, independently of one another: H, NO2, Cl, Br, F, I, R2-(L)n-Y—X—, OR, SR, NR2, R, NHCOR, CONHR, COOR, —CO—NH—(CH2)3—(O—CH2—CH2)3—CH2—NH—R2, —CO—NH—(CH2)3—(O—CH2—CH2)4—CH2—NH—R2 with R=alkyl or aryl, A is a linker arm comprising at least one covalent double bond enabling the conjugation of the diazo function with the aromatic ring and u is an integer between 0 and 2, preferably 0 or 1, —Y—X— represents —CONH—, —NHCO—, —CH2O—, —CH2S—, —Z— represents —NH—, —NHCO—, —CONH— or —O—, m is an integer between 1 and 10, preferably between 1 and 3, and p is an integer between 1 and 10, preferably between 1 and 3
    Type: Grant
    Filed: March 24, 2005
    Date of Patent: April 6, 2010
    Assignee: Biomerieux
    Inventors: Ali Laayoun, Eloy Bernal-Mendez
  • Patent number: 7678551
    Abstract: Generally, the present invention relates to lamotrigine analogs that have substituents at the triazine 3-position and on the benzene 4-position and 5-position. The lamotrigine analogs can include immunogenic moieties that can be used to prepare anti-lamotrigine antibodies, or antigenic moieties that can be used in immunodiagnostic assays for lamotrigine. Also, the lamotrigine analog can include tracer moieties for detecting the presence or amount of the analog during an immunodiagnostic assay. Additionally, the lamotrigine analogs can be used in immunodiagnostic assays to compete with lamotrigine for binding with anti-lamotrigine antibodies.
    Type: Grant
    Filed: October 20, 2005
    Date of Patent: March 16, 2010
    Assignee: Seradyn, Inc.
    Inventors: Anlong Ouyang, Lili Arabshahi, Mark Roberts, Melissa Wall
  • Patent number: 7662644
    Abstract: The invention provides peptide synthons having protected functional groups for attachment of desired moieties (e.g. functional molecules or probes). Also provided are peptide conjugates prepared from such synthons, and synthon and conjugate preparation methods including procedures for identifying optimum probe attachment sites. Biosensors are provided having functional molecules that can locate and bind to specific biomolecules within living cells. Biosensors can detect chemical and physiological changes in those biomolecules as living cells are moving, metabolizing and reacting to its environment. Methods are included for detecting GTP activation of a Rho GTPase protein using polypeptide biosensors. When the biosensor binds GTP-activated Rho GTPase protein, an environmentally sensitive dye emits a signal of a different lifetime, intensity or wavelength than when not bound.
    Type: Grant
    Filed: February 12, 2007
    Date of Patent: February 16, 2010
    Assignee: The Scripps Research Institute
    Inventors: Klaus M. Hahn, Alexei Toutchkine, Rajeev Muthyala, Vadim Kraynov, Steven J. Bark, Dennis R. Burton, Chester Chamberlain
  • Patent number: 7655429
    Abstract: Topiramate analogs have substituents at the sulfamate group, 9-position, or 10-position. Topiramate analogs may include immunogenic moieties to prepare anti-topiramate antibodies, or antigenic moieties for immunodiagnostic assays. Also, the topiramate analog can include tracer moieties for detecting the presence or amount of the analog during an immunodiagnostic assay. Additionally, the topiramate analogs can be used in immunodiagnostic assays to compete with topiramate for binding with anti-topiramate antibodies. Such an immunodiagnostic assay can be used for detecting the presence of topiramate in a sample obtained from a subject previously administered topiramate by the following: combining an anti-topiramate antibody and a topiramate analog with a sample to form a first composition; allowing any free topiramate from the sample and the topiramate analog to compete for binding with the antibody; detecting binding between the topiramate analog and the antibody.
    Type: Grant
    Filed: September 20, 2007
    Date of Patent: February 2, 2010
    Assignee: Seradyn, Inc.
    Inventors: Anlong Ouyang, Lili Arabshahi
  • Patent number: 7649085
    Abstract: Activated haptens useful for generating immunogens to HIV protease inhibitors, immunogens useful for producing antibodies to HIV protease inhibitors, and antibodies and labeled conjugates useful in immunoassays for the HIV protease inhibitor saquinavir. The novel haptens feature an activated functionality at the central, non-terminal hydroxyl group. Also described are monoclonal antibodies specific for saquinavir having less than 10% cross-reactivity with lopinavir, nelfinavir, amprenavir, ritonavir, and indinavir, and a murine hybridoma producing said antibodies.
    Type: Grant
    Filed: May 26, 2006
    Date of Patent: January 19, 2010
    Assignee: Roche Diagnostics Operations, Inc.
    Inventors: Gerald F. Sigler, Raymond A. Hui, Ina Deras, Richard Terry Root, Erasmus Huber, Herbert W. Von Der Eltz
  • Patent number: 7638291
    Abstract: Generally, the present invention relates to topiramate analogs that have substituents at the sulfamate group or at the 9-position or 10-position. The topiramate analogs can include immunogenic moieties that can be used to prepare anti-topiramate antibodies, or antigenic moieties that can be used in immunodiagnostic assays for topiramate. Also, the topiramate analog can include tracer moieties for detecting the presence or amount of the analog during an immunodiagnostic assay. Additionally, the topiramate analogs can be used in immunodiagnostic assays to compete with topiramate for binding with anti-topiramate antibodies.
    Type: Grant
    Filed: October 20, 2005
    Date of Patent: December 29, 2009
    Assignee: Seradyn, Inc.
    Inventors: Anlong Ouyang, Lili Arabshahi
  • Patent number: 7635598
    Abstract: In one aspect, the invention provides fluorescent probes and assays. The probes include a fluorophore-quencher pair that undergoes a switch from dark to fluorescent in response to a reaction of the quencher. The switch of the probe from dark to fluorescent is typically mediated by an enzyme that acts directly or indirectly on the quencher, interfering with its ability to quench fluorescence emission from the fluorophore. In another aspect, the invention provides a reporter gene assay system and methods of using this system. The assay system includes a fluorophore-quencher probe and an enzyme that acts directly or indirectly on the quencher, increasing the fluorescent emission of the fluorophore. In still other aspects, the invention provides nucleic acid constructs and cells expressing the peptide products of these constructs. In assays of the invention, the presence of a target substance is detected by the switching of fluorescence mediated by the change in oxidation state of the quencher.
    Type: Grant
    Filed: July 8, 2005
    Date of Patent: December 22, 2009
    Assignee: Biosearch Technologies, Inc.
    Inventors: Ronald M. Cook, Eliana Saxon Armstrong, Hans E. Johansson
  • Patent number: 7569678
    Abstract: Activated haptens useful for generating immunogens to HIV protease inhibitors, immunogens useful for producing antibodies to HIV protease inhibitors, and antibodies and labeled conjugates useful in immunoassays for the HIV protease inhibitor saquinavir. The novel haptens feature an activated functionality at the central, non-terminal hydroxyl group. Also described are monoclonal antibodies specific for saquinavir having less than 10% cross-reactivity with lopinavir, nelfinavir, amprenavir, ritonavir, and indinavir, and a murine hybridoma producing said antibodies.
    Type: Grant
    Filed: January 31, 2007
    Date of Patent: August 4, 2009
    Assignee: Roche Diagnostics Operations, Inc.
    Inventors: Gerald F. Sigler, Raymond A. Hui, Ina Deras, Erasmus Huber, Herbert W. Von Der Eltz, Sigrun Metz, Peter Kern
  • Patent number: 7566549
    Abstract: The present invention provides hapten derivatives useful for the preparation of antigens, antibodies and reagents for use in immunoassays for the detection of LSD and 2-oxo-3-hydroxy LSD. In the present invention, the 2-oxy LSD nucleus is derivatized out of the indole nitrogen to form an aminoalkyl derivative. The resulting haptens can then be further modified at this functionalized position for linking to appropriate immunogenic or labeling groups to provide reagents for immunoassays having substantially equal specificity for both LSD and 2-oxo-3-hydroxy-LSD.
    Type: Grant
    Filed: December 14, 2006
    Date of Patent: July 28, 2009
    Assignee: Roche Diagnostics Operations, Inc.
    Inventors: Mitali Ghoshal, Gerald F. Sigler, Alan J. McNally
  • Patent number: 7560556
    Abstract: Methods for generating chemiluminescence rapidly by reaction of at least one compound comprising a C—C double bond substituted at one carbon with two sulfur atom-containing groups with a peroxidase enzyme and a peroxide are disclosed. The chemiluminescence thus produced can be used as a detectable signal in assays for peroxidase enzymes or peroxide-producing enzymes and in assays employing enzyme-labeled specific binding pairs. Use of the methods provides rapid signal generation, achieving a plateau intensity in under one minute. The substrate can be provided in a composition which demonstrates unexpectedly long storage stability.
    Type: Grant
    Filed: March 4, 2005
    Date of Patent: July 14, 2009
    Assignee: Lumigen, Inc.
    Inventors: Hashem Akhavan-Tafti, Renuka de Silva, Wenhua Xie