Abstract: A rAAV vector is described herein which has an AAVhu68 capsid and at least one expression cassette in the capsid. The at least one expression cassette comprises nucleic acid sequences encoding a functional SMN protein and expression control sequences that direct expression of the SMN sequences in a host cell. Also provided are compositions containing this rAAVhu68.SMN vector and methods of using same for spinal muscular atrophy in a patient.
Type:
Grant
Filed:
February 27, 2018
Date of Patent:
February 14, 2023
Assignee:
The Trustees of the University of
Pennsylvania
Inventors:
James M. Wilson, Christian Hinderer, Nathan Katz, Qiang Wang
Abstract: Compositions and methods are provided for treating Leber congenital amaurosis (LCA) in a subject. In one aspect, a recombinant adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding Lebercilin. In another aspect, Lebercilin has an amino acid sequence of SEQ ID NO: 1. In yet another aspect, the nucleic acid molecule has a sequence of SEQ ID NO: 3 or a variant thereof. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.
Type:
Grant
Filed:
March 1, 2018
Date of Patent:
January 31, 2023
Assignee:
The Trustees of the University of Pennsylvania
Inventors:
Jean Bennett, Jeannette Bennicelli, Junwei Sun, Ji Yun Song, Sergei Nikonov
Abstract: Dosage units consist of an autologous cell therapy product composed of fibroblasts grown for each individual to be treated. The suspension of autologous fibroblasts, grown from a biopsy of each individual's own skin using current good manufacturing practices (CGMP), and standard tissue culture procedures, is supplied in vials containing cryopreserved fibroblasts or precursors thereof, having a purity of at least 98% fibroblasts and a viability of at least 85%, for administration of from one to six mL, preferably two mL, of cells at a concentration of from 1.0-2.0×107 cells/mL. When injected into the nasolabial fold wrinkles (creases on the sides of the nose that extend to the corners of the mouth), the autologous fibroblasts are thought to increase the synthesis of extracellular matrix components, including collagen, reducing the severity of these wrinkles. Dosage and timing of administration have been demonstrated to be critical to achieving clinically significant outcomes.
Abstract: Regimens useful in reducing the frequency of apheresis in a human patient having familial hypercholesterolemia are described. The method involves administering to the human subject via a peripheral vein by infusion of a suspension of replication deficient recombinant adeno-associated virus (rAAV).
Type:
Grant
Filed:
February 20, 2018
Date of Patent:
January 17, 2023
Assignee:
The Trustees of the University of
Pennsylvania
Abstract: A recombinant vector having an expression cassette is provided which comprises a modified human low density lipoprotein receptor (hLDLR) gene is provided, wherein said hLDLR gene encodes a modified hLDLR comprising (a) one or more of the following amino acid substitutions: L318H, N295D, H306D, V307D, N309A, D310N, L318H, and/or L318D; or (b) an amino acid substitution of any of (a) in combination with one or more of the following amino acid substitutions: K796, K809R and/or C818A. Also provided are pharmaceutical compositions containing this vector and uses therefor in lowering cholesterol and/or treating familial hypercholesterolemia.
Type:
Grant
Filed:
April 24, 2015
Date of Patent:
January 17, 2023
Assignee:
The Trustees of the University of Pennsylvania
Inventors:
James M. Wilson, Daniel J. Rader, Suryanrayan Somanathan
Abstract: Compositions and regimens useful in treating type I citrullenemia are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human Argininosuccinate Synthase 1 (ASS1).
Type:
Grant
Filed:
February 1, 2018
Date of Patent:
December 27, 2022
Assignee:
The Trustees of the University of
Pennsylvania
Inventors:
James M. Wilson, Jenny Agnes Sidrane, Lili Wang
Abstract: Provided herein are binding molecules, such as those that recognize or bind a peptide epitope of a cancer antigen, such as expressed on a cancer cell, including cells infected with human papilloma virus (HPV) or that contain HPV DNA sequences and/or those that recognize or bind a peptide epitope of HPV 16 E6 or E7, in the context of a major histocompatibility complex (MHC) molecule. Among the provided binding molecules are T cell receptors (TCRs) or antibodies, including antigen-binding fragments thereof, that bind or recognize such peptide epitopes. The present disclosure further relates to engineered cells comprising such binding molecules, e.g., TCRs or antibodies (and chimeric antigen receptors containing the antibodies), and uses thereof in adoptive cell therapy.
Type:
Grant
Filed:
April 3, 2019
Date of Patent:
October 18, 2022
Assignee:
Juno Therapeutics, Inc.
Inventors:
Stephen Jacob Goldfless, Brian Belmont, Cameron Brandt, Alexandra Croft, David Jeffrey Huss
Abstract: The present invention relates to nucleic acid regulatory elements that are able to enhance endothelial cell-specific expression of genes, methods employing these regulatory elements and uses of these elements. Expression cassettes and vectors containing these nucleic acid regulatory elements are also disclosed. The present invention is particularly useful for applications using gene therapy, more particularly endothelial cell-directed gene therapy, and for vaccination purposes.
Abstract: Provided herein are nucleic acids, recombinant adeno-associated viral particles, compositions and methods related to treating Friedreich's ataxia. In some examples, the nucleic acids, recombinant adeno-associated viral particles, compositions and methods involve us of a FXN coding sequence, a truncated FXN 3? UTR, and a prompter.
Type:
Grant
Filed:
July 1, 2021
Date of Patent:
September 20, 2022
Assignee:
University of Florida Research Foundation, Incorporated
Abstract: The present invention relates to a molecule delivery technology and a carrier technology, which may selectively deliver a material to a desired specific cell and living tissue. The present invention may be utilized in the field of a drug carrier which effectively delivers an imaging probe and a therapeutic agent to an affected part.
Type:
Grant
Filed:
August 12, 2019
Date of Patent:
September 20, 2022
Assignee:
KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY
Inventors:
Dae Ro Ahn, Se Hoon Kim, Kyoung Ran Kim, Hyo Young Kim, Yong Deok Lee
Abstract: Compositions and methods for prevention of ovarian cancer recurrence and for the treatment of BRCA1/2-wild type ovarian cancer are disclosed herein. In some embodiments, the composition comprises an autologous tumor cell vaccine comprising cells genetically modified for furin knockdown and GM-CSF expression. In some embodiments, the method comprises administration of an autologous tumor cell vaccine prior to administration of a combination of the autologous tumor cell vaccine and atezolizumab. Also disclosed herein are methods for treating a cancer in an individual comprising a wild-type BRCA1 gene, a wild-type BRCA2 gene, or a combination thereof, and is identified as homologous recombination deficiency (HRD)-negative.
Abstract: The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 1800 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in retinal ganglion cells of a gene when operatively linked to a nucleic acid sequence coding for said gene.
Type:
Grant
Filed:
February 5, 2018
Date of Patent:
June 28, 2022
Assignee:
FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH
Abstract: A nucleic acid construct and an immune cell, which harbor nucleic acids encoding a CAR and nucleic acids encoding at least one anti-inflammatory or immunosuppressant protein and methods of using the same in treatment or amelioration of inflammation or immune-mediated autoimmunity are described.
Type:
Grant
Filed:
September 27, 2016
Date of Patent:
June 21, 2022
Assignee:
TRUSTEES OF DARTMOUTH COLLEGE
Inventors:
Charles L. Sentman, Benjamine H. Arellano
Abstract: Disclosed herein is a recombinant nucleic acid, comprising: a mitochondrial targeting sequence; a mitochondrial protein coding sequence, wherein said mitochondrial protein coding sequence encodes a polypeptide comprising a mitochondrial protein; and a 3?UTR nucleic acid sequence. Also disclosed is a pharmaceutical composition comprising the recombinant nucleic acid and a method of treating Leber's hereditary optic neuropathy (LHON) using the pharmaceutical composition.
Type:
Grant
Filed:
February 22, 2021
Date of Patent:
June 7, 2022
Assignee:
Wuhan Neurophth Biotechnology Limited Company
Abstract: The present invention provides for nucleic acids improved for the expression of interleukin-15 (IL-15) in mammalian cells. The invention further provides for methods of expressing IL-15 in mammalian cells by transfecting the cell with a nucleic acid sequence encoding an improved IL-15 sequence. The present invention further provides expression vectors, and IL-15 and IL 15 receptor alpha combinations (nucleic acid and protein) that increase IL-15 stability and potency in vitro and in vivo. The present methods are useful for the increased bioavailability and biological effects of IL-15 after DNA, RNA or protein administration in a subject (e.g. a mammal, a human).
Type:
Grant
Filed:
August 21, 2019
Date of Patent:
May 24, 2022
Assignee:
THE UNITED STATES OF AMERICA, AS REPRESENTED BY, THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Abstract: The invention provides novel compositions, methods, and therapeutic uses related to fusogenic protein MINION (microprotein inducer of fusion).
Abstract: The invention provides compositions and methods for the preparation, manufacture and therapeutic use of viral vectors, such as adeno-associated virus (AAV) particles having viral genomes encoding one or more antibodies or antibody fragments or antibody-like polypeptides, for the prevention and/or treatment of diseases and/or disorders.
Abstract: The present invention relates to a combined preparation comprising (i) a modulator of pyruvate kinase M2 (PKM2) activity, and (ii) an agent providing high mobility group box 1 (HMGB1) polypeptide or a derivative thereof. The present invention also relates to the aforesaid combined preparation for use as a medicament and for use in the treatment of inappropriate cellular proliferation, preferably in the treatment of cancer. Moreover, the present invention relates to a method for determining whether a subject suffering from inappropriate cellular proliferation is amenable to a treatment comprising administration of a modulator of PKM2 activity as the only PKM2 inhibitor and to treatment methods related thereto.
Abstract: Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.
Type:
Grant
Filed:
March 1, 2021
Date of Patent:
March 8, 2022
Assignee:
Precision BioSciences, Inc.
Inventors:
Derek Jantz, James Jefferson Smith, Michael G. Nicholson, Daniel T. MacLeod, Jeyaraj Antony, Victor Bartsevich
Abstract: The invention relates to factors that influence or regulate homologous recombination, methods to monitor these factors, the use of these factors to screen for agents that modulate homologous recombination, and methods to activate or modulate homologous recombination.
Type:
Grant
Filed:
March 1, 2016
Date of Patent:
March 1, 2022
Assignee:
Sinai Health System
Inventors:
Daniel Durocher, Alexandre Orthwein, Sylvie Noordermeer