Abstract: The present disclosure relates to the genetically modified non-human animals that have a disruption at the endogenous CD132 gene (e.g., CD132 knockout), and methods of use thereof.
Abstract: The invention provides genetically modified non-human animals that express chimeric human/non-human T cell co-receptor polypeptides (e.g., CD4, CD8?, CD8?), as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same.
Type:
Grant
Filed:
October 6, 2017
Date of Patent:
November 3, 2020
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Lynn Macdonald, Andrew J. Murphy, Naxin Tu, Vera Voronina, Cagan Gurer
Abstract: The present invention provides compositions and methods for generating a genetically modified T cells comprising a chimeric antigen receptor (CAR) having an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the T cell exhibits prolonged exponential expansion in culture that is ligand independent and independent of the addition of exogenous cytokines or feeder cells.
Type:
Grant
Filed:
June 21, 2018
Date of Patent:
October 13, 2020
Assignee:
The Trustees of the University of Pennsylvania
Inventors:
Matthew J. Frigault, Yangbing Zhao, John Scholler, Carl H. June
Abstract: The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular against Preferentially Expressed Antigen of Melanoma (PRAME). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and TAA binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of TAA expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.
Abstract: The invention relates to the use of a CITED4 polypeptide and/or a microRNA-222 or precursor (e.g., pre-miR-222) or mimic thereof, for treating a cardiovascular disease or pathological condition, such as heart failure, myocardial infarction, and for promoting post-myocardial infarction cardiac remodeling in heart tissue.
Type:
Grant
Filed:
November 18, 2014
Date of Patent:
September 15, 2020
Assignees:
Beth Israel Deaconess Medical Center, Inc., Children's Medical Center Corporation
Inventors:
Anthony Rosenzweig, Vassilios J. Bezzerides
Abstract: This present invention relates to transgenic animals useful to study human diseases. Specifically, the invention relates to transgenic animals expressing at least two human proteins (optionally in replacement of the counterpart proteins in the animal) whereas a first human protein interacts with a second human protein. The transgenic animals can then be used for evaluating drugs or building disease models that are related to the expressed human proteins in the animals. The animals and methods disclosed herein reduce the possibility identifying a false-positive compound—the compound that show an effect in a naturally-occurring, non-transgenic animal but may not necessarily work or be therapeutic in human, since the compound may only interrupt the interaction between two animal proteins not necessarily two related human proteins.
Abstract: Provided herein, inter alia, are non-human animals comprising nucleic acid sequences encoding a C3 protein that comprises a human sequence as well as transgenic non-human animals comprising a C3 gene that is human in whole or in part as well as methods for using the same to screen for candidate therapeutic molecules to treat complement-related nephropathies. Also provided herein are methods for improving kidney function in an individual diagnosed with or thought to have a complement-related nephropathy.
Type:
Grant
Filed:
February 26, 2018
Date of Patent:
September 8, 2020
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Kishor Devalaraja-Narashimha, Lori Morton, Yifan Luo, Cong Huang, Karolina Meagher, Sarah Casanova
Abstract: The present invention provides methods and compositions for the remote control of cell function based on the use of a magnetic field to excite paramagnetic nanoparticles targeted to specific cell types. The cell type of interest expresses an ion channel wherein excitation of the paramagnetic nanoparticles results in a physical change that is transduced into a cellular response. Such cellular responses may include, for example, increases in gene expression resulting in production of one or more physiologically active proteins. The expression of such proteins can be used to treat a variety of different inherited or acquired diseases or disorders in a subject.
Type:
Grant
Filed:
March 21, 2017
Date of Patent:
September 8, 2020
Assignees:
THE ROCKEFELLER UNIVERSITY, RENSSELAER POLYTECHNIC INSTITUTE
Inventors:
Sarah Stanley, Jeffrey Friedman, Jonathan S. Dordick, Jeremy Sauer
Abstract: Methods and systems for generating MGE precursor cells in vitro as well as compositions of enriched MGE precursor cells are provided. The methods and systems provide efficient production of MGE precursors. The methods and systems disclosed herein provide functional MGE precursors which differentiate into functional GABAergic interneurons.
Type:
Grant
Filed:
September 10, 2018
Date of Patent:
September 1, 2020
Assignee:
The Regents of the University of California
Inventors:
Cory R. Nicholas, John L. Rubenstein, Arnold R. Kriegstein, Arturo Alvarez-Buylla
Abstract: The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular against Preferentially Expressed Antigen of Melanoma (PRAME). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and TAA binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of TAA expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.
Abstract: This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention provides a method to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene. The viral vector delivers the transgene to a region of the deep cerebellar nuclei region of the brain. Also provided are compositions and methods to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene to the motor cortex region of the subject's brain.
Type:
Grant
Filed:
November 2, 2007
Date of Patent:
August 18, 2020
Assignee:
GENZYME CORPORATION
Inventors:
James Dodge, Lamya Shihabuddin, Marco Passini, Seng H. Cheng, Catherine O'Riordan
Abstract: The present invention relates generally to the fields of immunology and vaccine technology. More specifically, the invention relates to recombinant human adenovirus vectors for delivery of avian immunogens and antigens, such as avian influenza into avians. The invention also provides methods of introducing and expressing an avian immunogen in avian subjects, including avian embryos, as well as methods of eliciting an immunogenic response in avian subjects to avian immunogens.
Type:
Grant
Filed:
November 28, 2017
Date of Patent:
August 18, 2020
Assignees:
Altimmune Inc., Auburn University
Inventors:
De-Chu C. Tang, Kent R. Van Kampen, Haroldo Toro
Abstract: The present invention relates to nucleic acid regulatory elements that are able to enhance muscle-specific expression of genes, in particular expression in cardiac muscle and/or skeletal muscle, 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 muscle-directed gene therapy, and for vaccination purposes.
Abstract: A method of radiation-free hematopoietic stem cell (HSC) transplantation comprises administering to a mammalian subject one or two doses of 2 to 10 mg/kg body weight of a purine base analog, such as 6TG as a pre-conditioning step. The method further comprises engrafting into the subject hypoxanthine-guanine phosphoribosyltransferase (HPRT)-deficient donor HSCs within 48 to 72 hours of the pre-conditioning step; and administering to the subject about 1 to 5 mg/kg of the purine base analog every two to four days for two to eight weeks following the engrafting step. The method is performed in the absence of pre-conditioning via radiation. The subject is therefore not treated with myeloablative radiation in preparation for transplantation, and thus the subject is free of myeloablative radiation-induced toxicity.
Type:
Grant
Filed:
February 1, 2019
Date of Patent:
July 14, 2020
Assignee:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Inventors:
Noriyuki Kasahara, Robert H. Schiestl, Katrin Hacke, Akos Szakmary, Gay M. Crooks
Abstract: The invention relates, in one aspect, generally to novel concept of guided selection of antibody variable domains, combination and expression entirely in vivo. An application is to produce multivalent polypeptides. The present invention relates to multivalent (eg, multispecific) antibodies, antibody chains and polypeptides, as well as heavy chain-only antibodies (H2 antibodies) that are devoid of light chains. The invention further relates to the selection, maturation and production of these in vivo in non-human vertebrates and non-human vertebrate cells. To this end the invention also relates to such non-human vertebrates and cells. The invention also relates to the provision of means to produce and select heavy chain-only antibodies and heavy chains comprising variable domains that have undergone affinity maturation.
Type:
Grant
Filed:
November 17, 2014
Date of Patent:
June 2, 2020
Assignee:
Kymab Limited
Inventors:
Volker Germaschewski, E-Chiang Lee, Hanif Ali, Jasper Clube
Abstract: Non-mammalian, transgenic animals, e.g., flies, that include a RAS transgene, are provided. Also provided are methods of using the subject transgenic non-mammalian animals to identify compounds having activity with respect to cellular proliferative, such as neoplastic, diseases.
Type:
Grant
Filed:
August 19, 2014
Date of Patent:
May 26, 2020
Assignee:
Tosk, Inc.
Inventors:
Travis Karg, William A. Garland, Steve Yanofsky
Abstract: The present invention relates to the transient modification of cells. In particular embodiments, the cells are immune systems, such as PBMC, PBL, T (CD3+ and/or CD8+) and Natural Killer (NK) cells. The modified cells provide a population of cells that express a genetically engineered chimeric receptor which can be administered to a patient therapeutically. The present invention further relates to methods that deliver mRNA coding for the chimeric receptor to unstimulated resting PBMC, PBL, T (CD3+ and/or CD8+) and NK cells and which delivers the mRNA efficiently to the transfected cells and promotes significant target cell killing.
Abstract: Provided is a method for determining a TCR polypeptide chain that can form a TCR specific for a peptide of interest. Also provided are methods and compositions for producing a cell expressing a T cell receptor (TCR) specific for a peptide of interest, methods and compositions for producing a TCR chain nucleic acid and/or pair of TCR chain polypeptides and/or nucleic acids encoding a TCR, a cell population comprising the cell harboring the nucleic acids encoding a TCR obtained by said method, and a method for treating a disorder comprising administering to the subject said cell population.
Abstract: This disclosure provides non-human animal models for age-related disorders and age-sensitive traits, particularly those caused by senescence-inducing stimuli, wherein the models comprise transgenes selectively expressed by senescent cells. The disclosure further provides methods for identifying therapeutic agents effective for treating or preventing age-related disorders and age-sensitive traits using the animal models, therapeutic agents identified using such methods, pharmaceutical compositions comprising the identified therapeutic agents, and methods of treating or preventing age-related disorders and age-sensitive traits.
Type:
Grant
Filed:
January 12, 2018
Date of Patent:
May 19, 2020
Assignee:
Buck Institute for Research on Aging
Inventors:
Marco Demaria, Francis Rodier, Remi-Martin Laberge, Judith Campisi
Abstract: The present disclosure pertains to a compositions and combinations for simultaneous, separate or sequential use which comprises (a) an oncolytic vaccinia virus that expresses a cytokine and a carboxylesterase enzyme, and, preferably, (b) a cancer co-drug, and to their uses for the treatment of cancer.