Modification Of Viruses (e.g., Attenuation, Etc.) Patents (Class 435/173.3)
-
Patent number: 6548242Abstract: The present invention concerns the product produced by inactivating extracellular or intracellular pathogenic virus in a biological composition without incurring substantial disruption or inactivation of cells and without significant loss of labile proteins or other valuable biological components also contained therein, the inactivation process comprising subjecting said composition to a virucidally effective amount of irradiation in the presence of (a) a mixture of a compound that quenches type I photodynamic reactions and a compound that quenches type II photodynamic reactions or (b) a bifunctional compound that is capable of quenching both type I and type II reactions, to thereby inactivate said virus while retaining functionality of said composition. The composition is advantageously subjected to the irradiation and the mixture of compounds or bifunctional compound in the presence of an irradiation sensitizer.Type: GrantFiled: January 10, 2001Date of Patent: April 15, 2003Assignee: New York Blood CenterInventors: Bernard Horowitz, Bolanle Williams, Henrietta Margolis-Nunno, Sing N. Chin
-
Publication number: 20030032176Abstract: The present invention relates to a method for producing helper-free stocks of recombinant adeno-associated virus (rAAV) which can be used to efficiently and stably transduce foreign genes into host cells or organisms. The method comprises the cotransfection of eukaryotic cells with rAAV and with helper AAV DNA in the presence of helper virus (e.g. adenovirus or herpesvirus) such that the helper AAV DNA is not associated with virion formation. The crux of the invention lies in the inability of the helper AAV DNA to recombine with rAAV vector, thereby preventing the generation of wild-type virus.Type: ApplicationFiled: September 24, 2002Publication date: February 13, 2003Applicant: THE TRUSTEES OF PRINCETON UNIVERSITYInventors: Thomas E. Shenk, Richard Jude Samulski, Long-Sheng Chang
-
Patent number: 6509020Abstract: A promising approach for the therapeutic treatment of brain tumors utilizes replication-competent, neuroattenuated herpes simplex virus-1 (HSV-1) mutants. This approach requires mutation of HSV-1 to eliminate killing of normal, non-dividing cells of the brain (e.g., neurons). The present invention discloses methods for killing malignant brain tumor cells in vivo entails providing replication competent herpes simplex virus vectors to tumor cells. A replication competent herpes simplex virus vector, with defective expression of the gamma 34.5 gene and the uracil DNA glycosylase (UNG) gene, specifically destroys tumor cells, is hypersensitive to anti-viral agents, and is not neurovirulent.Type: GrantFiled: September 22, 1999Date of Patent: January 21, 2003Assignee: The University of CincinnatiInventors: Richard Brent Pyles, Linda Marie Parysek, Ronald E. Warnick
-
Patent number: 6492148Abstract: The present invention relates to a method for the adaptation of infectious bursal disease viruses (IBDV) to growth in CEF cell culture. Changing the codons for amino acid residues 253 (Gln) and 284 (Ala) to 253 (His) and 284 (Thr) allowed bursa adapted Classical and Variant-E IBDV to grow in CEF cell culture. For GLS IBDV only a change of the codon for amino acid residue 284 was necessary.Type: GrantFiled: February 25, 2000Date of Patent: December 10, 2002Assignee: Akzo Nobel NVInventors: Adriaan Antonius Wilhelmus Maria van Loon, Egbert Mundt
-
Patent number: 6479280Abstract: The invention relates to a genetically modified bacteriophage, pseudovirion or phagemid capable of entering a host cell by binding of its artificial ligand to an artificial receptor present on said host cell. The invention relates also to the use of the genetically modified bacteriophage, pseudovirion or phagemid and of the host cell to screen sequence libraries, including antibody library.Type: GrantFiled: November 3, 1999Date of Patent: November 12, 2002Assignee: Vlaams Interuniversitair Institutuut voor Biotechnologie VZWInventors: Serge Muyldermans, Jan Steyaert, Karen Silence, Els Torreele
-
Patent number: 6455286Abstract: Psoralen compound compositions are synthesized which have primaryamino substitutions on the 3-, 4-, 5-, and 8-positions of the psoralen, which yet permit their binding to nucleic acid of pathogens. Reaction conditions that photoactivate these psoralens result in the inactivation of pathogens which contain nucleic acid. The compounds show similar activity in test systems to 4′ and 5′ derivatives of proralen useful for inactivation of pathogens in blood products. In addition to the psoralen compositions, the invention contemplates such inactivating methods using the new psoralens.Type: GrantFiled: February 9, 2000Date of Patent: September 24, 2002Assignee: Cerus CorporationInventors: Susan Wollowitz, Aileen Nerio
-
Patent number: 6448281Abstract: A compound of the formula I: wherein: X is CH or N; Y is O or S; Z is OH, NH2, NMeR3, NHR3; OR3 or 5- or 6-membered heterocycle, having 1 to 4 heteroatoms selected from O, N and S, said heterocycle being optionally substituted with from 1 to 4 substituents; A is N, COR7 or CR5, wherein R5 is H, halogen, or (C1-6) alkyl and R7 is H or (C1-6 alkyl), with the proviso that X and A are not both N; R6 is H, halogen, (C1-6 alkyl) or OR7, wherein R7 is H or (C1-6 alkyl); R1 is selected from the group consisting of 5- or 6-membered heterocycle having 1 to 4 heteroatoms selected from O, N, and S, phenyl, phenyl(C1-3)alkyl, (C2-6)alkenyl, phenyl(C2-6)alkenyl, (C3-6)cycloalkyl, (C1-6)alkyl, CF3, 9- or 10-membered heterobicycle having 1 to 4 heteroatoms selected from O, N and S, wherein said heterocycle, phenyl, phenyl(C2-6)alkenyl and phenyl(C1-3)alkyl), alkenyl, cycloalkyl, (C1-6)alkyl, and heterobicycle are all optionally substituted with from 1 to 4 substituents; R2 is selected from (C1-6)alkyl, (CType: GrantFiled: July 3, 2001Date of Patent: September 10, 2002Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Pierre Louis Beaulieu, Gulrez Fazal, James Gillard, George Kukolj, Volkhard Austel
-
Publication number: 20020119527Abstract: The invention relates to the coat proteins VP1 and VP2 of the human parovirus B19 and virus-like particles consisting of VP2 or of VP1 and VP2. The invention further comprises genetic information in the form of recombinant expression vectors which contain the genes coding for said proteins, and organisms which through genetic manipulation using such vectors have acquired the ability to produce such proteins and/or particles. The invention further comprises uses of such proteins and virus-like particles for diagnostics or vaccination.Type: ApplicationFiled: September 7, 2001Publication date: August 29, 2002Inventor: Caroline Sarah Brown
-
Patent number: 6413714Abstract: The present invention concerns a process for inactivating extracellular and intracellular virus in a biological composition without incurring substantial disruption or inactivation thereof, said process comprising subjecting said composition to a virucidally effective amount of UVA1 irradiation substantially in the absence of UVA2 irradiation for a period of time sufficient to thereby inactivate said virus while retaining functionality of said composition. The biological composition is advantageously a product that contains red blood cells or platelets. The process is advantageously carried out in the presence of an irradiation sensitizer compound and/or a quencher. The present invention also concerns the product substantially identical to that produced by the inventive process.Type: GrantFiled: May 26, 2000Date of Patent: July 2, 2002Assignee: New York Blood Center, Inc.Inventors: Henrietta Margolis-Nunno, Ehud Ben-Hur, Bernard Horowitz
-
Patent number: 6410013Abstract: Recombinant expression vectors and methods are provided for detecting HIV and monitoring HIV drug resistance.Type: GrantFiled: April 26, 2000Date of Patent: June 25, 2002Assignee: Musc Foundation for Research DevelopmentInventor: Jian-yun Dong
-
Publication number: 20020076773Abstract: The present invention discloses positive control material for nucleic acid amplification based detection of microorganisms in biological samples. The control material comprises purified microorganism that is rendered non-infectious but is amenable to nucleic acid amplification. Also disclosed is a process for making and using the control material.Type: ApplicationFiled: October 17, 2001Publication date: June 20, 2002Inventors: Gregory R. Chiklis, James C.D. Hengal
-
Patent number: 6387670Abstract: The invention concerns a method for producing recombinant virus. This method is based on the use of baculovirus for providing the complementary functions. It also concerns constructs used for implementing this method, the producing cells, and the resulting virus.Type: GrantFiled: May 18, 1999Date of Patent: May 14, 2002Assignee: Aventis Pharma, S.A.Inventors: Hélène Leblois-Prehaud, Michel Perricaudet, Emmanuelle Vigne, Patrice Yeh
-
Publication number: 20020034734Abstract: The invention concerns a pharmaceutical composition for treating or preventing C hepatitis (HCV), induced infections, which in a preferred embodiment, comprises a main active principle, (i) a fusion polypeptide, including the HCV capsid polypeptide (C191) and polypeptide coat (E1) and in which at least one cleavage site 173/174 and 191/192 has been made inoperative by mutation; (ii) an equimolar mixture of the C191 polypeptide of which the cleavage site 173/174 has been made inoperative and of the E1 polypeptide (mixture equivalent to the fusion polypeptide); or (iii) a DNA molecule coding for this fusion polypeptide. Products (i) to (iii) are characterized in that the C191 element is incapable of regulating the functioning of the genes, in particular of causing them to interact. Such a composition can also include any form equivalent to the products described above.Type: ApplicationFiled: July 26, 2001Publication date: March 21, 2002Applicant: Pasteur Merieux Serums & VaccinsInventor: Veronique Barban
-
Publication number: 20020034796Abstract: Compositions, methods and systems are provided for the stimulation of biological activities within stem cells by applying electromagnetic stimulation to an electroactive material, wherein the electromagnetic stimulation is coupled to the electromagnetic material. In general the present invention involves attaching or associating the desired cells to or with a surface comprising an electroactive material, and applying electromagnetic radiation directly to the desired area. In preferred embodiments, the stimulation of biological activities within cells results from inducing one or more activities including, but not limited to, gene expression, cell growth, cell differentiation, signal transduction, membrane permeability, cell division, contraction, and cell signaling.Type: ApplicationFiled: January 2, 2001Publication date: March 21, 2002Inventors: Venkatram Shastri, Ivan Martin, Robert Langer, Nahid Rahman
-
Patent number: 6303362Abstract: In vitro methods for making a recombinant adenoviral genome, as well as kits for practicing the same and the recombinant adenovirus vectors produced thereby, are provided. In the subject methods, the subject genomes are prepared from first and second vectors. The first vector includes an adenoviral genome having an E region deletion and three different, non-adenoviral restriction endonuclease sites located in the E region. The second vector is a shuttle vector and includes an insertion nucleic acid flanked by two of the three different non-adenoviral restriction endonucleases sites present in the first vector. Cleavage products are prepared from the first and second vectors using the appropriate restriction endonucleases. The resultant cleavage products are then ligated to produce the subject recombinant adenovirus genome. The subject adenoviral genomes find use in a variety of application, including as vectors for use in a variety of applications, including gene therapy.Type: GrantFiled: October 27, 1999Date of Patent: October 16, 2001Assignees: The Board of Trustees of the Leland Stanford Junior University, University of WashingtonInventors: Mark A. Kay, Hiroyuki Mizuguchi
-
Patent number: 6294361Abstract: The present invention concerns a process for inactivating an extracellular lipid enveloped human pathogenic virus and/or an intracellular human pathogenic virus which may be present in a blood cell composition containing ≧1×109 cells/ml by contacting that composition with a virucidally effective amount of at least one photoreactive compound having an absorption maximum of ≧630 nm, light and oxygen and/or a quencher. In one embodiment of the invention, the process is conducted under conditions whereby a structural integrity of greater than 80% of at least one type of blood cell contained within said composition is retained.Type: GrantFiled: October 26, 1997Date of Patent: September 25, 2001Assignee: New York Blood Center, Inc.Inventors: Bernard Horowitz, Jay E. Valinsky, Nicholas E. Geacintov, Bolanle Williams, Shanti B. Rywkin, Henrietta Nunno
-
Patent number: 6284249Abstract: The invention concerns a pharmaceutical composition for treating or preventing C hepatitis (HCV), induced infections, which in a preferred embodiment, comprises a main active principle, (i) a fusion polypeptide, including the HCV capsid polypeptide (C191) and polypeptide coat (E1) and in which at least one cleavage site 173/174 and 191/192 has been made inoperative by mutation; (ii) an equimolar mixture of the C191 polypeptide of which the cleavage site 173/174 has been made inoperative and of the E1 polypeptide (mixture equivalent to the fusion polypeptide); or (iii) a DNA molecule coding for this fusion polypeptide. Products (i) to (iii) are characterized in that the C191 element is incapable of regulating the functioning of the genes, in particular of causing them to interact. Such a composition can also include any form equivalent to the products described above.Type: GrantFiled: September 2, 1999Date of Patent: September 4, 2001Assignee: Pasteur Merieux Sérums & VaccinsInventor: Véronique Barban
-
Patent number: 6274324Abstract: Small specific binding molecules, such as single variable domain antibodies (Dabs) and Fv fragments, can be coupled to solid plastics surfaces or to tracers such as enzymes by means of linkers comprising polypeptides containing from 5 to 20 amino acids and which are hydrophobic and/or contain at least one lysine residue. The coupling can be achieved without significant loss of specific binding activity. The combined Dab/linker or Fv/linker can be prepared by expression in genetically-modified organisms.Type: GrantFiled: April 12, 1994Date of Patent: August 14, 2001Assignee: Unilever Patent Holdings B.V.Inventors: Paul James Davis, Martine Elisa Verhoeyen, Ronald Frank Jacobus De Winter
-
Patent number: 6258577Abstract: Methods and apparatuses are provided for inactivation of microorganisms in a fluid containing blood or blood products and comprising biologically active proteins. The method includes the steps of adding an effective, non-toxic amount of an endogenous photosensitizer to the fluid; exposing the fluid to photoradiation sufficient to activate the endogenous photosensitizer; and allowing the activated endogenous photosensitizer to interfere with nucleic acid present in microorganisms in the fluid so that the microorganisms are inactivated. Isoalloxazines and K- and L-vitamins are among the preferred photosensitizers.Type: GrantFiled: July 21, 1998Date of Patent: July 10, 2001Assignee: Gambro, Inc.Inventors: Raymond Paul Goodrich, Jr., Frank Corbin, III, Edward C. Wood, Jr.
-
Patent number: 6251644Abstract: A method is presented for inactivating non-enveloped viruses that may be contaminating a biological solution or suspension by mixing the solution or suspension with a photosensitizer to form a mixture, adjusting the operating conditions of the mixture so as to increase the permeability of the viruses to the photosensitizer, and then irradiating the adjusted mixture.Type: GrantFiled: November 22, 1994Date of Patent: June 26, 2001Assignee: Baxter International, Inc.Inventors: Samuel O. Sowemimo-Coker, Raymond P. Goodrich, Jr.
-
Patent number: 6238899Abstract: A method for altering or affecting ionic interactions in systems containing an unhydrated ion in a chemical or biological system comprising controlling the orientation and varying the intensity and fluctuation frequency of perpendicular or perpendicular and parallel paired static and sinusoidally varying magnetic fields so as to create magnetic interactions between ions and the molecules with which the ions are associated. Using the ion parametric resonance (IPR) model of the present invention, the magnetic fields can be adjusted to control precisely the desired orientation, intensity and fluctuation frequency of the magnetic fields.Type: GrantFiled: February 10, 1999Date of Patent: May 29, 2001Assignee: The United States of America as represented by the Environmental Protection AgencyInventors: Carl F. Blackman, Janie P. Blanchard
-
Patent number: 6235508Abstract: Viral and bacterial contaminants present in biological solutions are inactivated by mixing one of a novel class of photosensitizer with said solution and irradiating the mixture. Quinoline and quinolone compounds are useful as photosensitizers in this method. With certain photosensitizers a blocking agent may also be employed.Type: GrantFiled: September 15, 1998Date of Patent: May 22, 2001Assignee: Baxter International Inc.Inventors: Samuel O. Sowemimo-Coker, Nagender Yerram, Raymond P. Goodrich, Jr., Matthew S. Platz
-
Patent number: 6214354Abstract: Herpes Zoster, or varicella related post herpetic neuralgia is alleviated by immunizing people at risk of developing herpes zoster with varicella zoster virus (VZV) antigen.Type: GrantFiled: August 11, 1999Date of Patent: April 10, 2001Assignee: Merck & Co., Inc.Inventors: Gary B. Calandra, Philip J. Provost, Myron J. Levin, C. Jo White
-
Patent number: 6214534Abstract: The present invention concerns the product produced by inactivating extracellular or intracellular pathogenic virus in a biological composition without incurring substantial disruption or inactivation of cells and without significant loss of labile proteins or other valuable biological components also contained therein, the inactivation process comprising subjecting said composition to a virucidally effective amount of irradiation in the presence of (a) a mixture of a compound that quenches type I photodynamic reactions and a compound that quenches type II photodynamic reactions or (b) a bifunctional compound that is capable of quenching both type I and type II reactions, to thereby inactivate said virus while retaining functionality of said composition. The composition is advantageously subjected to the irradiation and the mixture of compounds or bifunctional compound in the presence of an irradiation sensitizer.Type: GrantFiled: May 24, 1996Date of Patent: April 10, 2001Assignee: New York Blood Center, Inc.Inventors: Bernard Horowitz, Bolanle Williams, Henrietta Margolis-Nunno, Sing N. Chin
-
Patent number: 6193980Abstract: Constructs for the delivery of sequences of interest to cells include a herpes virus latency active promoter (LAP) of the latency associated transcript (LAT) region. An internal ribosome entry site (IRES) is located downstream of the LAP, with a nucleotide sequence of interest downstream of the IRES. Stable, long-term expression including export of mRNA to the cytoplasm and translation of the encoded polypeptide, is found in neuronal and non-neuronal cells.Type: GrantFiled: September 17, 1997Date of Patent: February 27, 2001Assignee: Cambridge University Technical Services, LimitedInventors: Stacey Efstathiou, Robin H. Lachmann
-
Patent number: 6187572Abstract: A method is provided for inactivating viral and/or bacterial contamination in blood cellular matter, such as erythrocytes and platelets, or protein fractions. The cells or protein fractions are mixed with chemical sensitizers, frozen or freeze-dried, and irradiated with, for example, UV, visible, gamma or X-ray radiation while in the solid state.Type: GrantFiled: April 14, 1993Date of Patent: February 13, 2001Assignee: Baxter International Inc.Inventors: Matthew S. Platz, Raymond P. Goodrich, Jr., Nagender Yerram
-
Patent number: 6169109Abstract: Viral and bacterial contaminants present in biological solutions are inactivated by mixing one of a novel class of photosensitizer with said solution and irradiating the mixture.Type: GrantFiled: September 4, 1998Date of Patent: January 2, 2001Assignee: Baxter International Inc.Inventors: Sang Chul Park, Raymond P. Goodrich, Jr., Nagender Yerram, Samuel O. Sowemimo-Coker, Matthew S. Platz, Brian M. Aquila