Abstract: In accordance with the present invention, a method for increasing the yield of rLV vector particles comprising a trans gene encoding a therapeutic protein or fragment thereof is disclosed. In one approach, cells are transfected with plasmids encoding the necessary components for rLV production using a calcium chloride transfection mix at pH 7.1 wherein the calcium chloride and plasmids form a complex which is added to the cells at a constant speed. The cells are then incubated for a suitable time period wherein virus particle media is collected at least twice during the incubation period and stored in a cold storage unit, thereby reducing virus inactivation.
Type:
Grant
Filed:
August 27, 2018
Date of Patent:
November 7, 2023
Assignee:
The Children's Hospital of Philadelphia
Inventors:
Katherine A. High, John Fraser Wright, Bernd Hauck, Guang Qu
Abstract: Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.
Type:
Grant
Filed:
June 22, 2020
Date of Patent:
October 31, 2023
Assignee:
LENTIGEN TECHNOLOGY, INC.
Inventors:
Rimas J. Orentas, Dina Schneider, Waleed M. Haso, Stefan Miltenyi, Boro Dropulic
Abstract: The present invention relates to RNA interference-based methods for inhibiting the expression of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding microRNAs that knock down the expression of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.
Type:
Grant
Filed:
March 12, 2019
Date of Patent:
October 31, 2023
Assignee:
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Inventors:
Scott Quenton Harper, Jian Liu, Sara Coppens, Lindsay Wallace
Abstract: The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof, Lysosomal Membrane Protein 2 (LIMP2), Prosaposin, or any combination of the foregoing. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.
Type:
Grant
Filed:
October 3, 2018
Date of Patent:
October 31, 2023
Assignee:
Prevail Therapeutics, Inc.
Inventors:
Asa Abeliovich, Laura Heckman, Herve Rhinn
Abstract: Inducible promoters for the coordinated expression of at least one heterologous gene in yeast and methods of using them are disclosed. In particular, the invention relates to sets of inducible promoters derived from S. cerevisiae and related species that can be induced in the presence of nonfermentable carbon sources.
Type:
Grant
Filed:
February 20, 2020
Date of Patent:
October 24, 2023
Assignee:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
Colin Harvey, Ulrich Schlecht, Maureen Elizabeth Hillenmeyer
Abstract: Provided herein are methods for identifying high potency genomic insulator elements that can be used in a vector composition e.g., that are useful for preventing unwanted expression of neighboring genes, such as proto-oncogenes, when administered to a subject in need thereof. Also provided herein are methods for treating disease and methods for administering a nucleic acid to a subject using such vectors.
Type:
Grant
Filed:
January 31, 2020
Date of Patent:
October 17, 2023
Assignee:
UNIVERSITY OF WASHINGTON
Inventors:
George Stamatoyannopoulos, John Stamatoyannopoulos
Abstract: The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding an immunomodulatory polypeptide (e.g., a pro-inflammatory cytokine such as a human IL-2 or IL-12 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of cancer, such as lung cancer); and articles of manufacture or kits thereof.
Type:
Grant
Filed:
April 1, 2022
Date of Patent:
October 10, 2023
Assignee:
Krystal Biotech, Inc.
Inventors:
Suma Krishnan, Trevor Parry, Dana Michelle Previte, Mary Jane Duermeyer
Abstract: Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more cells of the retina for the treatment of retinal disorders and diseases.
Type:
Grant
Filed:
December 21, 2022
Date of Patent:
September 26, 2023
Assignee:
4D Molecular Therapeutics Inc.
Inventors:
David H. Kirn, Melissa Kotterman, David Schaffer
Abstract: The present disclosure provides rAAV vectors and rAAV virions that specifically express exogenous nucleic acid sequences in CD14+ cells. The rAAV vectors or virions are useful for specifically expressing exogenous nucleic acid sequences encoding, for example, cancer antigens, viral antigens, and/or bacterial antigens in monocytes and dendritic cells. The rAAV transduced CD14+ cells can be used as antigen presenting cells that induce antigen-specific T cell responses. The present disclosure further provides methods producing rAAV virions and methods of immunotherapy.
Abstract: The present invention relates to gene therapy delivery and expression systems comprising at least one helper-dependent adenoviral vector containing a nucleic acid sequence encoding for proteoglycan 4 (PRG4) or a biologically active fragment thereof. The invention further relates to a pharmaceutical composition comprising a therapeutically effective amount of at least one helper-dependent adenoviral vector containing said nucleic acid sequence encoding for proteoglycan 4 (PRG4), or a homolog thereof from any other species, or a biologically active fragment thereof. The invention also relates to the use of the novel gene therapy delivery and expression system according to the invention for use in the prevention and/or treatment of camptodactyly-arthropathy-coxa vara-pericarditis (CACP), or a musculoskeletal disorder such as a joint disorder or joint disease.
Abstract: Provided herein are methods of treating phenylketonuria by normalizing levels of amino acids, neurotransmitters, and neurotransmitter metabolites in a subject having phenylketonuria.
Type:
Grant
Filed:
May 8, 2019
Date of Patent:
August 29, 2023
Assignee:
BIOMARIN PHARMACEUTICAL INC.
Inventors:
Geoffrey Berguig, Rajeev Mahimkar, Hassibullah Akeefe, Peter Colosi
Abstract: The present invention relates to Adeno-associated virus type 9 methods and materials useful for intrathecal delivery of polynucleotides. Use of the methods and materials is indicated, for example, for treatment of lower motor neuron diseases such as SMA and ALS as well as Pompe disease and lysosomal storage disorders. It is disclosed that administration of a non-ionic, low-os-molar contrast agent, together with a rAA9 vector for the expression of Survival Motor Neuron protein, improves the survival of SMN mutant mice as compared to the administration of the expression vector alone.
Type:
Grant
Filed:
June 4, 2018
Date of Patent:
August 22, 2023
Assignees:
NATIONWIDE CHILDREN'S HOSPITAL, OHIO STATE INNOVATION FOUNDATION
Inventors:
Brian K. Kaspar, Arthur Burghes, Paul Porensky
Abstract: A method is provided to enhance repair or regeneration of a mammalian cardiovascular system to include heart and/or vasculature comprising: administering to a mammal in need thereof a composition comprising an effective amount of an agent that elevates levels of Smo, Ptc1, Shh, Ihh, Dhh, Gli1, Gli2, or Mycn.
Type:
Grant
Filed:
July 23, 2019
Date of Patent:
August 15, 2023
Assignee:
Regents of the University of Minnesota
Inventors:
Daniel J. Garry, Mary G. Garry, Bhairab Singh
Abstract: The technology described herein is directed to compositions comprising components of multi-component CALs or CARs, e.g., a TCR recognition domain; and one or both of: (a) an intracellular signaling domain; and (b) a first-type protein interaction domain. Further provided herein are methods for treating or preventing an autoimmune disease, a transplant rejection, or graft versus host disease.
Type:
Grant
Filed:
October 16, 2020
Date of Patent:
August 15, 2023
Assignees:
TRUSTEES OF BOSTON UNIVERSITY, THE GENERAL HOSPITAL CORPORATION
Inventors:
Mohammadreza Pakyari, Wilson Wong, Atsushi Okuma, Curtis Cetrulo
Abstract: The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.
Type:
Grant
Filed:
March 3, 2017
Date of Patent:
August 8, 2023
Assignees:
MEMORIAL SLOAN-KETTERING CANCER CENTER, UNIVERSITY OF WASHINGTON
Inventors:
Michel Sadelain, Isabelle Riviere, Jorge Mansilla-Soto, Xiuyan Wang, George Stamatoyannopoulos, John Stamatoyannopoulos, Mingdong Liu
Abstract: A method of preparing a recombinant adeno-associated virus (rAAV) including: (1) preparing a shuttle plasmid and a corresponding recombinant bacmid including a baculovirus genome, where the shuttle plasmid includes at least an rAAV gene of interest flanked by inverted terminal repeats (ITR-GOI) integrated with a heterologous functional gene fragment, and the recombinant bacmid includes an expression cassette of functional protein components necessary for assembly of the rAAV; (2) integrating the rAAV ITR-GOI and the expression cassette of functional protein components by using the shuttle plasmid and the recombinant bacmid, to yield a recombinant bacmid including a recombinant baculovirus genome; and (3) transfecting, with the recombinant bacmid, a host cell line.
Type:
Grant
Filed:
June 28, 2019
Date of Patent:
July 25, 2023
Assignee:
WUHAN INSTITUTE OF PHYSICS AND MATHEMATICS, CHINESE ACADEMY OF SCIENCES
Inventors:
Yang Wu, Fuqiang Xu, Ting Mei, Liangyu Jiang, Zengpeng Han
Abstract: Provided herein is a method of reprogramming a non-neuronal cell to a neuron. Aspects of the present disclosure relate to using cell reprogramming agent suppresses the expression or activity of PTB to convert a non-neuronal cell into a neuron. Also provided herein is a method of treating neurodegenerative disease by reprogramming non-neuronal cells in vivo to functional neurons.
Type:
Grant
Filed:
August 6, 2020
Date of Patent:
July 18, 2023
Assignee:
The Regents of the University of California
Abstract: The invention provides adeno-associated virus (AAV) Factor VIII (FVIII)-encoding/expressing vectors and virus, including AAV FVIII vectors with high expression activity and AAV FVIII vectors that express full-length or truncated functional FVIII protein. The invention also relates to methods of making the herein described AAV FVIII vectors, recombinant AAV FVIII virus particles comprising or expressing such vectors, associated pharmaceutical formulations comprising the same and therapeutic uses thereof.
Type:
Grant
Filed:
November 6, 2019
Date of Patent:
July 4, 2023
Assignee:
BIOMARIN PHARMACEUTICAL INC.
Inventors:
Stuart Bunting, Peter Cameron Colosi, Erno Pungor
Abstract: Compositions can be used to stimulate growth of a hair shaft from a hair follicle. These compositions can include methylated polynucleotides useful in treatment of autoimmune diseases or conditions, including those, such as alopecia areata, that result in hair loss.