Patents Examined by Gerald G Leffers, Jr.
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Patent number: 6541207Abstract: A method for in vitro construction of a library of recombined homologous polynucleotides from a number of different starting DNA templates and primers by induced template shifts during an polynucleotide synthesis is described, whereby A. extended primers are synthesized by a) denaturing the DNA templates b) annealing primers to the templates, c) extending the said primers by use of a polymerase, d) stop the synthesis, and e) separate the extended primers from the templates, B. a template shift is induced by a) isolating the extended primers from the templates and repeating steps A.b) to A.e) using the extended primers as both primers and templates, or b) repeating steps A.b) to A.e), C. this process is terminated after an appropriate number of cycles of process steps A. and B.a), A. and B.b), or combinations thereof. Optionally the polynucleotides are amplified in a standard PCR reaction with specific primers to selectively amplify homologous polynucleotides of interest.Type: GrantFiled: October 13, 2000Date of Patent: April 1, 2003Assignee: Novozymes A/SInventors: Jesper Vind, Torben Vedel Borchert
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Patent number: 6537784Abstract: This invention relates to chimeric nucleic acids and to the therapeutic induction of apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells the chimeric nucleic acid. The chimeric nucleic acid having at least one TNF&agr; promoter enhancer attached to a functional copy of a TNF&agr; promoter and further attached to at least one copy of an apoptosis-inducing gene, which is further attached to a 3′UTR. The apoptosis-inducing gene is Granzyme B. The invention also relates to methods of making and using self-regulated apoptosis chimeric nucleic acids and pharmaceutical compositions containing them for treating inflammatory diseases.Type: GrantFiled: January 12, 1999Date of Patent: March 25, 2003Assignee: Boehringer Ingelheim Pharmaceuticals Inc.Inventors: Revati J. Tatake, Steven D. Marlin, Randall W. Barton
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Patent number: 6537779Abstract: An improved T7 based promoter-driven protein expression system comprising an operator sequence downstream of the T7 promoter sequence, and having a further operator sequence upstream of the T7 promoter sequence.Type: GrantFiled: April 3, 2000Date of Patent: March 25, 2003Assignee: Zeneca LimitedInventors: Bhupendra Vallabh Kara, David Pioli, Kenneth Robert Bundell, Robert Craig Hockney
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Patent number: 6531307Abstract: The present invention provides recombinant viral vectors carrying a vector construct which directs the expression of a gene product (eg. HSVTK) that activates a compound with little or no cytotoxicity into a toxic product. Also provided are methods of destroying or inhibiting pathogenic agents in a warm blooded animal, comprising the step of administering to the animal a viral vector such as that described above, in order to inhibit or destroy the pathogenic agent.Type: GrantFiled: May 31, 1995Date of Patent: March 11, 2003Assignee: Chiron CorporationInventors: Jack R. Barber, Harry E. Gruber, Douglas J. Jolly
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Patent number: 6527689Abstract: The invention provides a human maternally transcribed protein (HMTP) and polynucleotides which identify and encode HMTP. The invention also provides expression vectors, host cells, agonists, antibodies and antagonists. The invention also provides methods for treating disorders associated with expression of HMTP.Type: GrantFiled: July 15, 1999Date of Patent: March 4, 2003Assignee: Incyte Genomics, Inc.Inventors: Jennifer L. Hillman, Preeti Lal, Neil C. Corley
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Patent number: 6525184Abstract: This invention relates to the therapeutic induction of apoptosis in activated inflammatory cells, or cells at a site of inflammation, by introducing into those cells a chimeric gene containing an apoptosis-inducing gene (AIG) driven by a promoter of an inducible gene activated in inflammation and a promoter enhancer such that the inflammatory cells are targeted. In one embodiment, the chimeric gene comprises at least one TNF&agr; promoter enhancer attached to a functional copy of a minimal TNF&agr; promoter and further attached to at least one copy of an apoptosis-inducing gene, wherein expression of the gene is driven by the TNF&agr; promoter. Attachment can be direct, distal, proximal or combinations thereof. Example apoptosis-inducing genes include caspase 3, caspase 4, caspase 5, Granzyme B. Advantageously, the TNFp-AIG chimeric gene is expressed in only those cells producing the inflammatory cytokine, TNF&agr;.Type: GrantFiled: February 27, 1998Date of Patent: February 25, 2003Assignee: Boehringer Ingelheim Pharmaceuticals, Inc.Inventors: Revati J. Tatake, Steven D. Marlin, Randall W. Barton
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Patent number: 6521457Abstract: A recombinant lentiviral vector expression system comprises a first vector that comprises a nucleic acid sequence of at least part of the Equine Infectious Anemia Virus (EIAV) genome. The vector contains at least one defect in at least one gene encoding an EIAV structural protein, but is preferably a gag/pol expression vector. The expression system further comprises a second vector, also comprising a nucleic acid sequence of at least part of the Equine Infectious Anemia Virus (EIAV) genome, and additionally containing a multiple cloning site wherein a heterologous gene may be inserted. The expression system also comprises a third vector which expresses a viral envelope protein. The first and third vectors are packaging signal-defective. When the expression system is transfected into a lentivirus-permissive cell, replication-defective EIAV particles may be produced, which particles are useful in delivering heterologous genes to a broad range of both dividing and non-dividing cells.Type: GrantFiled: July 6, 2001Date of Patent: February 18, 2003Assignee: University of North Carolina at Chapel HillInventor: John C. Olsen
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Patent number: 6521412Abstract: The present invention relates to complexes of the CDK2 protein with proteins identified as interacting with CDK2 by a modified yeast two hybrid assay system. The proteins identified to interact with CDK2 are cyclin H, cyclin I, ERH, and two gene products, hsReq*-1 and hsReq*-2, which are splice variants of the gene hsReq. Thus, the invention provides complexes of CDK2 and cyclin H, cyclin I, ERH, hsReq*-1, and hsReq*-2, and derivatives, fragments and analogs thereof. The invention also provides nucleic acids encoding the hsReq*-1 and hsReq*-2, and proteins and derivatives, fragments and analogs thereof. Methods of screening the complexes for efficacy in treating and/or preventing certain diseases and disorders, particularly cancer, atherosclerosis and neurodegenerative disease are also provided.Type: GrantFiled: June 22, 1999Date of Patent: February 18, 2003Assignee: CuraGen CorporationInventors: Meijia Yang, Krishnan Nandabalan, Vincent Peter Schulz
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Patent number: 6514726Abstract: Disclosed are Aspergillus fumigatus coenzyme-A carboxylase genes and polypeptides and their use in identifying antifungal agents, for example.Type: GrantFiled: December 30, 1999Date of Patent: February 4, 2003Assignee: Millennium Pharmaceuticals, Inc.Inventors: Patrick K. Dorr, Tanya Parkinson, Christine Ellen Bulawa
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Patent number: 6511828Abstract: A new family of proteins having structural similarity to the baculovirus inhibitor of apoptosis protein (iap) are described. These ilp's (iap-like proteins) are distinguished by the presence of a RING finger domain and three baculovirus iap-like repeat motifs. Exemplified are sequences from Drosophila and human. Methods for the use of these proteins, and nucleic acids coding therefor, are provided. These methods include both the inhibition and stimulation of apoptosis in target cells.Type: GrantFiled: May 31, 1996Date of Patent: January 28, 2003Assignee: Arch Development CorporationInventors: Craig B. Thompson, Colin S. Duckett
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Patent number: 6500943Abstract: The present invention provides a DNA having promoter activity of Tec tyrosine kinase and a vector having incorporated within it the promoter to thereby enable a high level expression of an exogenous gene in hematopoietic stem cells and hepatic cells.Type: GrantFiled: November 8, 2001Date of Patent: December 31, 2002Assignee: Dnavec Research Inc.Inventors: Hiroyuki Mano, Tsuneaki Sakata, Mamoru Hasegawa, Toshiaki Tabata
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Patent number: 6489116Abstract: Disclosed herein are methods for detecting multiple compounds in a sample, involving: (a) contacting the sample with a mixture of binding reagents, the binding reagents being nucleic acid-protein fusions, each having (i) a protein portion which is known to specifically bind to one of the compounds and (ii) a nucleic acid portion which encodes the protein portion and which includes a unique identification tag; (b) allowing the protein portions of the binding reagents and the compounds to form complexes; (c) capturing the binding reagent-compound complexes; (d) amplifying the nucleic acid portions of the complexed binding reagents; and (e) detecting the unique identification tag of each of the amplified nucleic acids, thereby detecting the corresponding compounds in the sample. Also disclosed herein are kits for carrying out such methods.Type: GrantFiled: January 4, 2001Date of Patent: December 3, 2002Assignee: Phylos, Inc.Inventor: Richard W. Wagner
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Patent number: 6485934Abstract: The invention relates to a regulation system for inducible expression of genes, comprising a lambdoid promoter, a gene coding for a repressor for the lambdoid promoter and a gene coding for an antirepressor of the repressor, which antirepressor is under the influence of an inducible promoter. The invention further relates to a regulatory replicon, comprising said gene coding for an antirepressor, an expression system, comprising said regulatory replicon, and an expression vector based on a lambdoid promoter, and also to a method for producing a gene product in a heterologous host, by providing a culture of a host comprising a heterologous sequence which codes for the gene product. Providing a culture of a host comprising a heterologous sequence is obtained by putting the expression of the heterologous sequence under the control of a regulation system, a gene coding for a repressor for the lambdoid promoter and a gene coding for an antirepressor, and by inducing the promoter of the antirepressor gene.Type: GrantFiled: October 22, 1999Date of Patent: November 26, 2002Inventors: Nico Maurice August Corneel Mertens, Eric Rene Remaut, Walter Charles Fiers
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Patent number: 6485966Abstract: A method for producing recombinant adeno-associated virus in the absence of contaminating helper virus or wild-type virus involves culturing a mammalian host cell containing an rAd/AAV hybrid virus, an AAV rep sequence and an AAV cap sequence under the control of regulatory sequences directing expression thereof. The rAd/AAV hybrid virus contains a rAAV construct to be packaged into an AAV virion in an backbone containing the adenoviral sequences necessary to express E1a and E1b gene products and to permit replication of the hybrid virus. The method of the invention permits replication of the hybrid virus and production of rAAV virion in this host cell in the absence of a helper virus and obviates a subsequent purification step to purify rAAV from contaminating virus.Type: GrantFiled: April 5, 2001Date of Patent: November 26, 2002Assignee: The Trustees of the University of PennsylvaniaInventors: Guangping Gao, James M. Wilson
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Patent number: 6479237Abstract: The aim of the invention is to use at least one conditional promoter to implement a method for detecting one or more proteins interacting directly or indirectly with at least two other proteins during the formation of a protein complex, or during the inhibition of the formation of a protein complex.Type: GrantFiled: February 23, 2000Date of Patent: November 12, 2002Assignees: Institut National de la Sante et de la Recherche Medicale (Inserm), Centre National de la Recherche Scientifique, Bristol-Myers Squibb CompanyInventors: Jacques Camonis, Francisco Romero-Portillo, Ricardo Attar, Jean-Marc Egly, Franck Tirode
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Patent number: 6479290Abstract: The invention concerns adenoviral vectors having the characteristic of containing a region essential for heterologous packaging with respect to the adenoviral genome from which they are derived. The invention also concern a method for making a viral preparation containing said adenoviral vectors, a cell, a pharmaceutical composition or material comprising them and their therapeutic or prophylactic use. Finally, the invention concerns an adenoviral genome of animal origin having attenuated packaging properties with respect tot he native genome from which it is derived.Type: GrantFiled: January 27, 2000Date of Patent: November 12, 2002Assignee: Transgene S. A.Inventors: Majid Mehtali, Monika Lusky, Arend Jan Winter
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Patent number: 6479292Abstract: The invention concerns the introduction of predetermined genetic changes in target genes of a living cell by introducing an oligodeoxynucleotide encoding the predetermined change. The oligodeoxynucleotides are effective in animal, plant and bacterial cells. Specific end modifications that greatly increase the effectiveness of the oligodeoxynucleotides in bacteria are described. Surprisingly, unmodified oligodeoxynucleotides can be as effective in mammalian cells, including in vivo hepatocytes, as the modified nucleotides and can be as effective or more effective than chimeric oligonucleotides that consist of a mixture of deoxynucleotides and 2′-O-methyl ribonucleotides.Type: GrantFiled: August 25, 2000Date of Patent: November 12, 2002Assignee: ValiGen (US), Inc.Inventors: Richard A. Metz, Bruce L. Frank, Debra M. Walther
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Patent number: 6475726Abstract: The invention comprises methods useful within a larger process for identifying compounds and/or designing further compounds with activity to produce a desired phenotype (for example, growth inhibition) in cells whose target cell component is the subject of certain studies to identify such compounds. The invention employs constructed cells comprising a regulable gene encoding a biomolecule which modulates (inhibits or activates) in vivo the function of a target component of the cell which can be an enzyme, for example, methionyl-tRNA synthetase of Staphylococcus aureus. The process incorporates methods for identifying biomolecules that bind to a chosen target cell component in vitro, methods for identifying biomolecules that also bind to the chosen target and modulate its function intracellularly, causing a phenotypic effect.Type: GrantFiled: June 25, 1999Date of Patent: November 5, 2002Assignee: Cubist Pharmaceuticals, Inc.Inventors: Francis P. Tally, Jianshi Tao, Philip A. Wendler, Gene Connelly, Paul L. Gallant, Xiaoyu Shen, Jiansu Zhang
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Patent number: 6472165Abstract: A selective modulatory retigabine binding potassium channel receptor site containing subunits KCNQ2 and KCNQ3, and a method for directly selectively modulating that receptor site by administering retigabine to a cell preparation of the potassium channel.Type: GrantFiled: August 3, 1999Date of Patent: October 29, 2002Assignee: Arzneimittelwerk Dresden GmbHInventors: Chris Rundfeldt, Rainer Netzer
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Patent number: 6472151Abstract: The present invention provides a method for generating and isolating cell lines that functionally express molecular targets for drug discovery without utilizing information from the nucleic acid or amino acid sequence of the target protein. This procedure for the first time allows one to develop fast, high throughput screens for evaluation of test compounds that may modulate molecular targets whose specific nucleic acid or amino acid sequences are unavailable.Type: GrantFiled: August 10, 1999Date of Patent: October 29, 2002Assignee: Bristol-Myers Squibb CompanyInventors: C. David Weaver, Todd A. Verdoorn, Gordon W. Robinson