Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise an immunoglobulin heavy chain locus that includes unrearranged human immunoglobulin light chain gene segments and an immunoglobulin light chain locus that includes a single rearranged human light chain variable region nucleotide sequence. The unrearranged human light chain gene segments may be operably linked to a heavy chain constant region nucleotide sequence and the rearranged human immunoglobulin light chain variable region nucleotide sequence may be operably linked to a light chain constant region nucleotide sequence. Also provided are methods for obtaining nucleic acid sequences that encode immunoglobulin light chain variable domains capable of binding an antigen in the absence of a cognate variable domain, and expressing such nucleic acid sequences in a host cell, e.g., to generate a multispecific antigen-binding protein.
Type:
Grant
Filed:
March 18, 2016
Date of Patent:
September 7, 2021
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Lynn Macdonald, Andrew J. Murphy, Cagan Gurer, Robert Babb
Abstract: Disclosed herein are methods, compositions, kits, and agents useful for inducing ? cell maturation, and isolated populations of SC-? cells for use in various applications, such as cell therapy.
Type:
Grant
Filed:
July 21, 2020
Date of Patent:
August 31, 2021
Assignee:
President and Fellows of Harvard College
Inventors:
Quinn P. Peterson, Felicia J. Pagliuca, Douglas A. Melton, Jeffrey R. Millman, Michael Saris Segel, Mads Gurtler
Abstract: The present provides fusion proteins comprising PDGF and VEGF binding portions, and recombinant viral particles encoding the fusion proteins. Compositions comprising the fusion proteins and viral particles as well as methods of using the same are also provided.
Type:
Grant
Filed:
November 20, 2018
Date of Patent:
August 10, 2021
Assignee:
GENZYME CORPORATION
Inventors:
Peter Pechan, Jeffery Ardinger, Hillard Rubin, Samuel Wadsworth, Abraham Scaria
Abstract: The present invention relates to a method for inducing the differentiation of corneal epithelial cells from pluripotent stem cells. More specifically, the present invention relates to a method for autonomously differentiating pluripotent stem cells, such as human iPS cells, into ectodermal cell lineage in a serum-free medium without using feeder cells and inducing the differentiation of the resultant ocular surface ectodermal lineage cells into corneal epithelial cells.
Abstract: The present invention relates to three-dimensional (3D) tissue constructs and methods of using such 3D tissue constructs to screen for neurotoxic agents. In particular, provided herein are methods of producing and using complex, highly uniform human tissue models comprising physiologically relevant human cells, where the tissue models have the degree of sample uniformity and reproducibility required for use in quantitative high-throughput screening applications.
Type:
Grant
Filed:
December 31, 2015
Date of Patent:
July 13, 2021
Assignee:
WISCONSIN ALUMNI RESEARCH FOUNDATION
Inventors:
James A. Thomson, William L. Murphy, Charles D. Page, Michael P. Schwartz, Zhonggang Hou
Abstract: The present invention provides apparatus and methods for production of tissue structures and organs. In some examples, a cleanspace facility may be equipped with modelling hardware and software, nanotechnology and microelectronic apparatus, and additive manufacturing equipment to print cells and support matrix to allow cells to grow into tissue structures and organs. Various methods relating to using and producing the tissue engineering system are discussed.
Type:
Grant
Filed:
June 5, 2018
Date of Patent:
June 29, 2021
Assignee:
Organofab Technologies, Inc.
Inventors:
Frederick A. Flitsch, Robert A. Flitsch, Brent Chanin, Rudiger Hilken
Abstract: This invention relates to a transgenic non-human mammal whose genome comprises a polynucleotide sequence encoding a T cell receptor that is specific to a fluorescent protein, where the T cell of the non-human mammal comprises the T cell receptor. The present invention also relates to an isolated T cell from the transgenic non-human mammal of the present invention, an isolated T cell comprising an expression construct comprising a polynucleotide sequence that encodes a T cell receptor that is specific to a fluorescent protein, methods of making transgenic non-human mammals comprising T cell receptors that are specific to a fluorescent protein, a method of depleting cells in a non-human mammal using isolated T cells that encode a T cell receptor that is specific to a target protein, and a method of characterizing a T cell response to an agent.
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:
March 31, 2020
Date of Patent:
June 15, 2021
Assignee:
Wuhan Neurophth Biological Technology Limited Company
Abstract: Provided herein are methods of preparing a poloxamer for use in a cell culture medium. Also provided herein are cell culture media containing the poloxamer prepared by the methods herein, as well as methods of using the media for cell culturing and polypeptide production from cells.
Type:
Grant
Filed:
September 22, 2016
Date of Patent:
June 15, 2021
Assignee:
Genentech, Inc.
Inventors:
Ganesh Prasadh Vissvesvaran, Robert David Kiss, Steven J. Meier, Inchan Kwon, Kara Calhoun, Kate Winchester, Amelia Adams, Marion Glenn, Stefan Koenig, Alan Deese
Abstract: Factor VIII variants and methods of use thereof are disclosed. In particular embodiments, Factor VIII variants are expressed more efficiently by cells over wild-type Factor VIII proteins, are secreted at increased levels by cells over wild-type Factor VIII proteins, exhibit enhanced activity over wild-type Factor VIII proteins and are packaged more efficiently into viral vectors.
Type:
Grant
Filed:
August 13, 2015
Date of Patent:
May 25, 2021
Assignee:
THE CHILDREN'S HOSPITAL OF PHILADELPHIA
Inventors:
Denise Sabatino, Katherine A. High, Liron Elkouby
Abstract: Disclosed herein are methods of generating induced pluripotent stem cells. The method involves providing a quantity of somatic or non-embryonic cells, contacting the contacting the somatic or non-embryonic cells with a quantity of one or more reprogramming factors and one or more RNA molecules, and culturing the somatic or non-embryonic cells for a period of time sufficient to generate at least one induced pluripotent stem cell. Various reprogramming factors and RNA molecules for use in the methods are disclosed herein. Also disclosed are cell lines and pharmaceutical compositions generated by use of the methods.
Abstract: Provided herein are methods and compositions for dynamically controlling and targeting multiple immunosuppressive mechanisms in cancer. Some aspects provide cells engineered to produce multiple effector molecules, each of which modulates a different immunosuppressive mechanisms of a tumor, as well as methods of using the cells to treat cancer, such as ovarian, breast, or colon cancer.
Type:
Grant
Filed:
October 17, 2019
Date of Patent:
May 4, 2021
Assignee:
SENTI BIOSCIENCES, INC.
Inventors:
Timothy Kuan-Ta Lu, Russell Morrison Gordley, Jack Tzu-Chiao Lin, Brian Scott Garrison, Philip Janmin Lee, Alba Gonzalez-Junca, Don-Hong Wang, Daniel Frimannsson
Abstract: An object of the present invention is to provide a novel medical application to regenerative medicine that uses pluripotent stem cells (Muse cells). The present invention provides a cell preparation for treating cerebral infarction and sequelae associated therewith that contains SSEA-3-positive pluripotent stem cells isolated from mesenchymal tissue in the body or cultured mesenchymal cells. The cell preparation of the present invention is based on a brain tissue regeneration mechanism by which Muse cells differentiate into nerve cells and the like in damaged brain tissue by administering Muse cells into cerebral parenchyma.
Type:
Grant
Filed:
January 23, 2017
Date of Patent:
May 4, 2021
Assignees:
LIFE SCIENCE INSTITUTE, INC., TOHOKU UNIVERSITY
Inventors:
Masanori Yoshida, Mari Dezawa, Teiji Tominaga
Abstract: The invention provides a method of producing a synthetic retina, comprising: i) providing a three dimensional stem cell culture throughout the differentiation time course, ii) differentiating the three dimensional stem cell culture for a first time period in a first neural cell culture medium comprising: a) L-glutamine; b) B27 supplement; and c) an IGF-1 receptor agonist, iii) subsequently differentiating the three dimensional stem cell culture for a second time period in a second neural cell culture medium comprising: a) L-glutamine; b) B27 supplement; c) N2 supplement; and d) an IGF-1 receptor agonist, wherein said synthetic retina contains laminated retinal tissue comprising.
Abstract: The invention provides a method for producing a retinal tissue by (1) subjecting pluripotent stem cells to floating culture in a serum-free medium containing a substance inhibiting the Wnt signal pathway to form an aggregate of pluripotent stem cells, (2) subjecting the aggregate to floating culture in a serum-free medium containing a basement membrane preparation, and then (3) subjecting the aggregate to floating culture in a serum-containing medium. The invention also provides a method for producing an optic-cup-like structure, a method for producing a retinal pigment epithelium, and a method for producing a retinal layer-specific neural cell.
Type:
Grant
Filed:
November 22, 2012
Date of Patent:
April 13, 2021
Assignees:
Sumitomo Chemical Company, Limited, RIKEN
Abstract: The invention provides in certain embodiments, a method of generating a re-programmed differentiated epithelial cell comprising (a) contacting a non-stem somatic cell obtained from a subject with an effective amount of a de-differentiation agent to form a de-differentiated cell, and (b) transfecting the de-differentiated cell with an expression cassette comprising a promoter operably linked to a nucleic acid encoding a conversion agent to form a re-programmed differentiated cell. The invention also provides in certain embodiments, a method of generating a re-programmed differentiated epithelial cell comprising (a) contacting a non-stem somatic cell obtained from a subject with an effective amount of a de-differentiation agent to form a de-differentiated cell, and (b) contacting the de-differentiated cell with a conversion agent to form a re-programmed differentiated cell.
Abstract: Disclosed herein are methods and compositions for modifying TCR genes, using nucleases (zinc finger nucleases or TAL nucleases) to modify TCR genes.
Type:
Grant
Filed:
March 26, 2018
Date of Patent:
February 16, 2021
Assignees:
Sangamo Therapeutics, Inc., Ospedale San Raffaele SRL
Inventors:
Philip D. Gregory, Michael C. Holmes, David Paschon, Lei Zhang, Maria Chiara Bonini, Pietro Genovese, Zulma Magnani, Sara Mastaglio, Luigi Naldini
Abstract: The invention generally features compositions comprising induced pluripotent stem cell progenitors (also termed reprogramming progenitor cells) and methods of isolating such cells. The invention also provides compositions comprising induced pluripotent stem cells (iPSCs) derived from such progenitor cells. Induced pluripotent stem cell progenitors generate iPSCs at high efficiency. In particular embodiments the invention is predicated upon increased expression of an estrogen related receptor and changes in the oxidative and glycolytic pathways.
Type:
Grant
Filed:
February 26, 2016
Date of Patent:
February 16, 2021
Assignee:
SALK INSTITUTE FOR BIOLOGICAL STUDIES
Inventors:
Ronald Evans, Michael Downes, Yasuyuki Kida, Teruhisa Kawamura, Zong Wei, Ruth T. Yu, Annette R. Atkins
Abstract: The purpose of the present invention is to provide a method of purification and preparation of cultured corneal endothelial cells, and in particular, to provide cell surface markers for use in corneal endothelial cells not including transformed cells. Provided are cell markers for distinguishing normal cells and transformed cells, in particular normal and transformed corneal endothelium cells. These cell markers relate to specific cell surface markers, for example, to a normal corneal endothelial surface marker such as CD166, and a transformed cell surface marker such as CD73. By using the transformed cell surface marker such as CD73 to remove transformed cells by sorting, it becomes possible to improve purity of a normal cultured corneal endothelium. By using normal corneal endothelial surface marker such as CD166, or by combined use with the transformed cell surface marker, it becomes possible to provide a means for verifying the purity of a prepared corneal endothelium.
Type:
Grant
Filed:
July 28, 2014
Date of Patent:
February 2, 2021
Assignees:
KYOTO PREFECTURAL PUBLIC UNIVERSITY CORPORATION, ACTUALEYES INC., CORNEAGEN. INC.
Abstract: Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.
Type:
Grant
Filed:
August 9, 2018
Date of Patent:
February 2, 2021
Assignee:
Regeneren Pharmaceuticals, Inc.
Inventors:
Lynn Macdonald, Sean Stevens, Andrew J. Murphy, Margaret Karow