Abstract: A potent short hairpin RNA (shRNA734) directed to human Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) improves the rate of gene-modified stem cell engraftment by a conditioning and in vivo selection strategy to confer resistance to a clinically available guanine analog antimetabolite, 6TG, for efficient positive selection of gene-modified stem cells. Uses for polynucleotides comprising the shRNA734 include methods for knocking down HPRT in a cell, for conferring resistance to a guanine analog antimetabolite in a cell, for producing selectable genetically modified cells, for selecting cells genetically modified with a gene of interest from a plurality of cells, for removing cells genetically modified with a gene of interest from a plurality of cells, and for treating a subject infected with HIV.
Type:
Grant
Filed:
February 17, 2017
Date of Patent:
July 5, 2022
Assignee:
THE REGENTS OF THE UNIVERSITY OE CALIFORNIA
Abstract: The present invention discloses a modified interleukin 12 (nsIL-12) and its gene, recombinant vector and use in manufacture of a medicament for treatment of tumors. When the oncolytic adenovirus vector carrying the modified interleukin 12 gene targets tumor tissue, the modified interleukin 12 is continuously expressed at a low level and mainly distributed in the local tumor tissue, which improves the specificity to tumor cells and reduces the systemic toxicity of interleukin 12; the modified interleukin 12 shows stronger inhibitory effect on tumor growth in intraperitoneally disseminated tumors and orthotopic tumors, and has low toxicity. The modified interleukin 12 armed oncolytic viruses show excellent anti-tumor effects, with a significant regression of tumors and lower toxicity compared with the existing IL-12 armed virus.
Type:
Grant
Filed:
September 9, 2016
Date of Patent:
May 31, 2022
Assignees:
BEIJING BIO-TARGETING THERAPEUTICS TECHNOLOGY INC., Zhengzhou University
Abstract: The invention relates to defective interfering viruses and defective interfering virus RNAs that are effective as antiviral agents. The invention also relates to methods for identifying defective interfering virus RNAs that can be used as effective antiviral agents.
Abstract: The present invention discloses a modified interleukin 12 (nsIL-12) and its gene, recombinant vector and use in manufacture of a medicament for treatment of tumors. When the oncolytic adenovirus vector carrying the modified interleukin 12 gene targets tumor tissue, the modified interleukin 12 is continuously expressed at a low level and mainly distributed in the local tumor tissue, which improves the specificity to tumor cells and reduces the systemic toxicity of interleukin 12; the modified interleukin 12 shows stronger inhibitory effect on tumor growth in intraperitoneally disseminated tumors and orthotopic tumors, and has low toxicity. The modified interleukin 12 armed oncolytic viruses show excellent anti-tumor effects, with a significant regression of tumors and lower toxicity compared with the existing IL-12 armed virus.
Type:
Grant
Filed:
September 9, 2016
Date of Patent:
April 19, 2022
Assignees:
BEIJING BIO-TARGETING THERAPEUTICS TECHNOLOGY INC., Zhengzhou University
Abstract: The present invention provides a means to modulate gene expression in vivo in a manner that avoids problems associated with CRISPR endogenous protein knock-out or knock-in strategies and strategies that provide for correction, or alteration, of single nucleotides. The invention includes inserting into the genome a nucleotide encoding a heterobifunctional compound targeting protein (dTAG) in-frame with the nucleotide sequence of a gene encoding an endogenously expressed protein of interest which, upon expression, produces an endogenous protein-dTAG hybrid protein. This allows for targeted protein degradation of the dTAG and the fused endogenous protein using a heterobifunctional compound.
Type:
Grant
Filed:
February 6, 2018
Date of Patent:
April 5, 2022
Assignee:
DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Dennis Buckley, Georg Winter, Andrew J. Phillips, Timothy Heffernan, James Bradner, Justin Roberts, Behnam Nabet
Abstract: The present invention relates to a nanoparticle for oral gene delivery, which is a novel oral gene delivery system capable of regulating blood glucose levels in biological systems and insulin secretion in response to ingested meals. More specifically, the present invention relates to a nanoparticle for gene delivery, comprising: an ionic polymer conjugated with bile acid or a bile acid derivative; and a gene; and to a pharmaceutical composition comprising the same.
Abstract: Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.
Type:
Grant
Filed:
June 12, 2020
Date of Patent:
March 8, 2022
Assignees:
Regents of the University of Minnesota, Intima Bioscience, Inc., The United States of America, as Represented by the Secretary, Department of Health and Human Services
Inventors:
Branden Moriarity, Beau Webber, Modassir Choudhry, Steven A. Rosenberg, Douglas C. Palmer, Nicholas P. Restifo
Abstract: Solutions, reagents, and methods for nucleic acid purification. In certain aspects, cationic surfactant and, optionally, an anionic surfactant solutions are provided which can be used for phase separation and capture of nucleic acids, such as plasmid or genomic DNA, to a solid phase carrier, such as a mineral matrix.
Type:
Grant
Filed:
April 25, 2018
Date of Patent:
February 1, 2022
Assignee:
ZYMO RESEARCH CORPORATION
Inventors:
Ryan Kemp, Jonathan A. Claypool, Marc E. Van Eden, Xi-Yu Jia
Abstract: Compositions comprising a polymeric micellar nanoparticle composition comprising a block or graft copolymer comprising at least one polycationic polymer and at least one polyethylene glycol (PEG) polymer having an average molecular weight less than 1 kDa, and at least one nucleic acid, wherein the graft or block copolymer and at least one nucleic acid are complexed and condensed into a shaped micellar nanoparticle that is stable in biological media are disclosed. The presently disclosed subject matter also provides a method for preparing the presently disclosed polymeric micellar nanoparticle compositions, a method for targeting at least one metastatic cancer cell in a subject, and a method for treating a disease or condition using the presently disclosed polymeric micellar nanoparticle compositions.
Type:
Grant
Filed:
February 7, 2018
Date of Patent:
February 1, 2022
Assignee:
The Johns Hopkins University
Inventors:
Hai-Quan Mao, John Michael Williford, Maani Archang, Il Minn, Yong Ren, Jose Luis Santos, Martin G. Pomper
Abstract: A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses a single light chain variable domain derived from a single rearranged light chain variable region gene in the germline of the non-human animal, wherein the single rearranged light chain variable region gene comprises a substitution of at least one non-histidine encoding codon with a histidine encoding codon. Methods of making non-human animals that express antibodies comprising a histidine-containing universal light chain are provided.
Type:
Grant
Filed:
July 14, 2016
Date of Patent:
December 7, 2021
Assignee:
Regeneran Pharmaceuticals, Inc.
Inventors:
John McWhirter, Lynn Macdonald, Andrew J. Murphy
Abstract: A synthetic, flexible tissue matrix and methods for repairing hyaline cartilage defects in a joint using the flexible tissue matrix are described. The flexible tissue matrix includes a high molecular weight polycaprolactone polymer entangled with a polysaccharide such as hyaluronic acid. In the methods, autologous bone mesenchymal stem cells are introduced to a joint by a microfracturing technique, and a membrane made of the flexible matrix is applied to the joint. Cartilage which forms in the joint is hyaline cartilage rather than fibrocartilage.
Type:
Grant
Filed:
March 14, 2019
Date of Patent:
November 30, 2021
Assignee:
Isto Technologies II, LLC
Inventors:
Mitchell S. Seyedin, Anthony J. Ward, Matthew Matava
Abstract: The present invention relates to the use of at least one tetra functional non-ionic amphiphilic block copolymer as a vehicle for capped or uncapped mRNA for intracellular delivery for gene therapy.
Type:
Grant
Filed:
April 1, 2015
Date of Patent:
November 23, 2021
Assignees:
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM), UNIVERSITE DE NANTES, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
Abstract: The present invention disclosed a method of fabricating an antibody immunolipoplex nanoparticle (Ab-ILN) biochip and antibody tethered lipoplex nanoparticle (Ab-TLN) biochip. The aforementioned antibody-based lipoplex nanoparticle biochip or the related array contains molecular probes and is applied for detecting the presence of a disease or condition in a subject obtaining a body fluid sample by capturing and identifying both membrane protein and intra-vesicular DNA/RNA/proteins of extracellular vesicles (EVs).
Type:
Grant
Filed:
January 11, 2016
Date of Patent:
November 16, 2021
Assignee:
SPOT BIOSYSTEMS LTD.
Inventors:
Ly James Lee, Kwang Joo Kwak, Andrew Lee
Abstract: This disclosure relates to recombinant cellular expression of chimeric proteins with peptide sequences derived from lymphocyte receptors and uses for treating cancer. In certain embodiments, the disclosure relates to a recombinant vector comprising a nucleic acid that encodes a chimeric protein with a segment with a targeting moiety based on a variable lymphocyte receptor (VLR) capable of binding a tumor associated antigen and a segment with a T cell signal transduction subunit. In certain embodiments, the recombinant vectors are used in immune based cancer treatments.
Type:
Grant
Filed:
May 1, 2019
Date of Patent:
October 5, 2021
Assignees:
Emory University, Children's Healthcare of Atlanta, Inc.
Inventors:
H. Trent Spencer, Christopher B. Doering, Brantley R. Herrin, Max Dale Cooper
Abstract: Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.
Abstract: The present invention relates to compositions and methods for the treatment of a canine CD20 positive disease or condition using a canine CD20-specific chimeric antigen receptor. One aspect includes a modified canine T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity in canine.
Type:
Grant
Filed:
July 8, 2016
Date of Patent:
September 14, 2021
Assignee:
The Trustees of the University of Pennsylvania
Inventors:
Nicola Mason, Daniel J. Powell, Jr., Mohammed Kazim Panjwani, Jenessa Smith
Abstract: The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.
Type:
Grant
Filed:
February 14, 2020
Date of Patent:
September 7, 2021
Assignee:
KSQ Therapeutics, Inc.
Inventors:
Micah Benson, Jason Merkin, Gregory V. Kryukov, Solomon Martin Shenker, Michael Schlabach, Noah Tubo
Abstract: Disclosed are compositions and methods for producing modified adeno-associated virus (AAV) cap genes and combinatorial libraries of chimeric AAV vectors and virions; selecting for virions displaying cell-specific tropisms; and, in certain embodiments, producing helper vectors containing one or more modified AAV cap genes. The synthetic combinatorial AAV capsid libraries of the invention are useful in introducing into selected target host cells one or more nucleic acid molecules. The viral vectors and genetic constructs disclosed herein are also useful in a variety of diagnostic and/or therapeutic gene-therapy regimens.
Type:
Grant
Filed:
December 3, 2018
Date of Patent:
August 17, 2021
Assignee:
University of Florida Research Foundation, Incorporated
Inventors:
Damien Marsic, Sergei Zolotukhin, Mavis Agbandje-McKenna
Abstract: Provided herein are methods for cell therapy by modifying transfused cells to express an inducible caspase 9 protein, so that the cells may be selectively killed if the patient experiences dangerous side effects. Provided also within relates in part to methods for preventing or treating Graft versus Host Disease by modifying T cells before administration to a patient, so that they may be selectively killed if GvHD develops in the patient.
Abstract: The disclosure is based on the finding that compounds capable of binding to (or interacting with) chromatin binding/remodelling complexes (for example Polycomb group PRC1 and Trithorax group MLL) and/or modulation of the same can be used to modulate (for example switch on/off) ciliogenesis as may occur, for example, in the human pulmonary bronchial epithelium. Provided are compounds, compositions, methods and medicaments which may be used to treat and/or prevent diseases and/or conditions associated with aberrant or defective ciliogenesis.
Type:
Grant
Filed:
November 17, 2016
Date of Patent:
August 3, 2021
Assignee:
Academisch Ziekenhuis Leiden a/u Leiden University Medical Center