Abstract: Disclosed are capsid-modified rAAV particles and expression vectors, as well as compositions and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and using novel capsid-protein-mutated particle or rAAV vector constructs in a variety of diagnostic and therapeutic applications including, inter alia, as delivery agents for diagnosis, treatment, or amelioration of one or more diseases, disorders, or dysfunctions of the mammalian eye. Also disclosed are methods for subretinal delivery of therapeutic gene constructs to mammalian photoreceptors and retinal pigment epithelial cells, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and/or in vivo applications including the treatment of a variety of inherited retinal diseases.
Type:
Grant
Filed:
March 4, 2015
Date of Patent:
June 4, 2019
Assignee:
University of Florida Research Foundation, Inc.
Inventors:
Shannon E. Boye, Sanford L. Boye, Mavis Agbandje-McKenna, Arun Srivastava
Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.
Type:
Grant
Filed:
April 30, 2010
Date of Patent:
May 14, 2019
Assignees:
Ospedale San Raffaele S.r.l., Fondazione Telethon
Inventors:
Alessandra Biffi, Bernhard Rudolf Gentner, Luigi Naldini
Abstract: A non-human animal model for neurodegenerative and/or inflammatory diseases is provided, which non-human animal comprises a disruption in a C9ORF72 locus. In particular, non-human animals described herein comprise a deletion of an entire coding sequence of a C9ORF72 locus. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)), autoimmune and/or inflammatory diseases (e.g., SLE, glomerulonephritis) are also provided.
Type:
Grant
Filed:
May 26, 2016
Date of Patent:
May 14, 2019
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Amanda Atanasio, Burcin Ikiz, Guochun Gong, Michael L. Lacroix-Fralish, Ka-man Venus Lai, David M. Valenzuela
Abstract: A process for producing a retroviral or lentiviral vector formulation comprising a filter-sterilisation step wherein the filter-sterilisation step is not the final step in the purification process.
Type:
Grant
Filed:
September 14, 2015
Date of Patent:
April 30, 2019
Assignee:
Oxford BioMedica (UK) Limited
Inventors:
Richard Truran, Robert Buckley, Pippa Radcliffe, James Miskin, Kyriacos Mitrophanous
Abstract: Embodiments of the invention concern copolymers and nanoparticles for use as delivery agents for one or more agents for therapy for a medical condition of humans and animals. Some of embodiments of the invention provide new reagents for biomedical research in cell culture, animal models and plants, for example. The copolymers comprise PLGA and PEI and, in some embodiments, also comprise 1-(3-aminopropyl)-4-methylpiperazine (APMP), Fc binding peptide and/or antibody. In certain embodiments, APMP-PLGA-PEI, Fc binding peptide/antibody-PLGA-PEI or Fc binding peptide/antibody-AP-MP-PLGA-PEI nanoparticles comprising one or more therapeutic agents are delivered to an individual in need thereof or used for biomedical research in cell cultures, animal models and plants.
Abstract: Systems and methods for detecting and/or identifying target cells (e.g., bacteria) using engineered transduction particles are described herein. In some embodiments, a method includes mixing a quantity of transduction particles within a sample. The transduction particles are associated with a target cell. The transduction particles are non-replicative, and are engineered to include a nucleic acid molecule formulated to cause the target cell to produce a series of reporter molecules. The sample and the transduction particles are maintained to express the series of the reporter molecules when target cell is present in the sample. A signal associated with a quantity of the reporter molecules is received. In some embodiments, a magnitude of the signal is independent from a quantity of the transduction particle above a predetermined quantity.
Type:
Grant
Filed:
December 22, 2016
Date of Patent:
March 26, 2019
Assignee:
GeneWeave Biosciences, Inc.
Inventors:
Diego Ariel Rey, Shaunak Roy, Leonardo Maestri Teixeira, Ryan C. Griswold, Kenneth G. Olson, Bruce J. Richardson, Victor H. Yee, Werner Frei
Abstract: Composition containing a microorganism, preferably an Archaea, expressing a TMA methyltransferase and a TMA methyl group acceptor corrinoid protein, capable of metabolizing trimethylamine (TMA) in the presence of hydrogen in a human cavity, such as the intestine or the vagina, for use as a medicament for treating, reducing or eliminating TMA at the level of the human cavity. In addition, a composition containing a TMA methyltransferase and a TMA methyl group acceptor corrinoid protein. These compositions are of use for treating trimethylaminuria, for treating vaginal fluids in the case of bacterial vaginosis and for reducing or eliminating odours due to TMA. These compositions are also of use for reducing the level of plasma TMAO, for preventing the formation of atheroma plaques and/or for preventing cardiovascular diseases.
Type:
Grant
Filed:
September 27, 2013
Date of Patent:
March 26, 2019
Assignee:
UNIVERSITE D'AUVERGNE CLERMONT I
Inventors:
Jean-François Brugere, Guillaume Borrel, Paul William O'Toole, Corinne Malpuech-Brugere, Monique Alric
Abstract: The present invention relates to compositions comprising a decellularized tissue. The present invention also provides an engineered three dimensional lung tissue exhibiting characteristics of a natural lung tissue. The engineered tissue is useful for the study of lung developmental biology and pathology as well as drug discovery.
Type:
Grant
Filed:
February 18, 2015
Date of Patent:
January 29, 2019
Assignee:
Yale University
Inventors:
Elizabeth Calle, Laura E. Niklason, Thomas Petersen, Liqiong Gui
Abstract: The present invention relates to production of proteins in insect cells whereby repeated coding sequences are used in baculoviral vectors. In particular the invention relates to the production of parvoviral vectors that may be used in gene therapy and to improvements in expression of the viral rep proteins that increase the productivity of parvoviral vectors.
Type:
Grant
Filed:
September 30, 2015
Date of Patent:
January 29, 2019
Assignee:
UniQure IP B.V.
Inventors:
Andrew Christian Bakker, Wilhelmus Theodorus Johannes Maria C Hermens
Abstract: The invention relates to an isolated nucleic acid molecule comprising at least one promoter that is active in fungal cells of the trichoderma species, wherein a nucleic acid sequence encoding an N-acetylglucosamine-2-epimerase and/or an N-acetylneuraminic acid synthase is operatively bound to each promoter. The at least one promoter that is active in fungal cells is a constitutive promoter.
Type:
Grant
Filed:
October 15, 2014
Date of Patent:
October 23, 2018
Assignee:
TECHNISCHE UNIVERSITÄT WIEN
Inventors:
Astrid Mach-Aigner, Robert Mach, Matthias G. Steiger
Abstract: A non-immunogenic selection epitope may be generated by removing certain amino acid sequences of the protein. For example, a gene encoding a truncated human epidermal growth factor receptor polypeptide (EGFRt) that lacks the membrane distal EGF-binding domain and the cytoplasmic signaling tail, but retains an extracellular epitope recognized by an anti-EGFR antibody is provided. Cells may be genetically modified to express EGFRt and then purified without the immunoactivity that would accompany the use of full-length EGFR immunoactivity. Through flow cytometric analysis, EGFRt was successfully utilized as an in vivo tracking marker for genetically modified human T cell engraftment in mice. Furthermore, EGFRt was demonstrated to have cellular depletion potential through cetuximab mediated antibody dependent cellular cytotoxicity (ADCC) pathways.
Abstract: The present invention relates generally to systems and methods for preparing, storing, shipping and using skin equivalents made by organotypic culture. In particular, the present invention relates to systems and methods for cryopreserving viable skin substitutes.
Type:
Grant
Filed:
March 13, 2014
Date of Patent:
October 9, 2018
Assignee:
Stratatech Corporation
Inventors:
B. Lynn Allen-Hoffmann, John C. Pirnstill, Kenneth R. Gratz, Allen R. Comer
Abstract: Aspects of the invention described herein relate to synthetic, modified RNAs and their use in vivo to modulate gene expression. Aspects of the invention further relate to the use of these synthetic, modified RNAs in myocytes, cardiomyoctes, and tumors.
Type:
Grant
Filed:
March 12, 2012
Date of Patent:
October 2, 2018
Assignees:
THE GENERAL HOSPITAL CORPORATION, CHILDREN'S MEDICAL CENTER CORPORATION
Inventors:
Kenneth R. Chien, Leon M. Ptaszek, Oi-Lan Lui, Lior Zangi, Wataru Ebina, Derrick J. Rossi
Abstract: The use of a purine nucleoside phosphorylase or nucleoside hydrolase or a vector encoding expression of one of these enzymes is detailed along with the use of a prodrug cleaved by the purine nucleoside phosphorylase or nucleoside hydrolase for the preparation of a direct injection inhibition of replicating or non-replicating targeted cells. The targeted cells do not normally express the introduced purine nucleoside phosphorylase or nucleoside hydrolase. The enzyme and prodrug are amenable to intermixing and injection as a single dose or as separate injection or administration to the targeted cells. The substance and prodrug efficacy are enhanced through exposure of the targeted cells to X-ray radiation. Administration of a prodrug regardless of administration route to the targeted cells is effective in combination with X-ray radiation therapy to kill or inhibit function of the targeted cells.
Type:
Grant
Filed:
February 20, 2012
Date of Patent:
September 25, 2018
Assignees:
SOUTHERN RESEARCH INSTITUTE, THE UAB RESEARCH FOUNDATION
Abstract: The present invention relates to fibrinogen preparations enriched in ?-extended fibrinogen. Compositions comprising such preparations show improved clotting properties compared to preparations based on HMW Fib which typically contain no or only low amounts of ?-extended fibrinogen. In particular, clot formation time and the clot strength of a clot made by ?-extended fibrinogen are improved. In addition, plasmin-mediated degradation of ?-extended fibrinogen is reduced as compared to plasma derived fibrinogen.
Type:
Grant
Filed:
June 5, 2017
Date of Patent:
June 26, 2018
Assignee:
Mallinckrodt Pharma IP Trading D.A.C.
Inventors:
Joseph Grimbergen, Jacob Koopman, Abraham Bout
Abstract: The present disclosure provides compositions and methods for the prevention or treatment of ocular neovascularization, such as AMD, in a human subject, by administering subretinally a pharmaceutical composition comprising a pharmaceutically effective amount of a vector comprising a nucleic acid encoding soluble Fms-related tyrosine kinase-1 (sFlt-1) protein to the human subject.
Type:
Grant
Filed:
December 21, 2017
Date of Patent:
June 26, 2018
Assignee:
Avalanche Australia Pty Ltd.
Inventors:
Ian J. Constable, P. Elizabeth Rakoczy, Chooi-May Lai, Thomas W. Chalberg, Jr.
Abstract: Methods and compositions for reducing expression of genes on Chromosome 21 (“Chr 21”) by targeting an XIST transgene to the Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene or a Regulator of calcineurin 1 (RCAN1) gene, and cells and transgenic animals comprising an XIST transgene inserted into a DYRK1A or RCAN1 allele, e.g., cells and animals trisomic for human Chr 21 and mouse Chr 16.
Type:
Grant
Filed:
March 14, 2014
Date of Patent:
June 26, 2018
Assignee:
University of Massachusetts
Inventors:
Jeanne B. Lawrence, Jun Jiang, Lisa L. Hall
Abstract: A method for inducing an immune response against HIV in a subject includes the step of preparing an HIV-1 gp120 envelope protein coding sequence particle having an N425K mutation, introducing the HIV-1 gp120 protein coding sequence particle having an N425K mutation into an expression construct using yeast homologous recombination, transfecting a cell with the expression construct, wherein the HIV-1 particle is secreted by the cell, and administering the secreted HIV-1 particle and a pharmaceutically acceptable carrier to the subject, wherein the secreted HIV-1 particle stimulates an immune response in the subject.
Abstract: This document provides methods and materials related to vesicular stomatitis viruses. For example, vesicular stomatitis viruses, nucleic acid molecules encoding VSV polypeptides, methods for making vesicular stomatitis viruses, and methods for using vesicular stomatitis viruses to treat cancer are provided.
Type:
Grant
Filed:
August 24, 2016
Date of Patent:
April 24, 2018
Assignee:
Mayo Foundation for Medical Education and Research
Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.
Type:
Grant
Filed:
August 31, 2017
Date of Patent:
April 24, 2018
Assignees:
Fondazione Telethon, Ospedale San Raffaele S.r.l.
Inventors:
Alessandra Biffi, Bernhard Rudolf Gentner, Luigi Naldini