Patents Examined by Michael C. Wilson
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Patent number: 11617783Abstract: The present application provides materials and methods for treating a patient with a titin-based myopathy, particularly a titin-based cardiomyopathy, and/or other titinopathy. In addition, the present application provides materials and methods for editing the titin gene in a cell by genome editing.Type: GrantFiled: November 15, 2016Date of Patent: April 4, 2023Assignee: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITALInventors: Louise Rodino-Klapac, Rachael Potter
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Patent number: 11613735Abstract: A method for inducing reprogramming of a cell of a first type which is not a non-hepatocyte (non-hepatocyte cell), into a cell with functional hepatic drug metabolizing and transporting capabilities, is disclosed. The non-hepatocyte is induced to express or overexpress hepatic fate conversion and maturation factors, cultured in somatic cell culture medium, hepatocyte cell culture medium and hepatocyte maturation medium for a sufficient period of time to convert the non-hepatocyte cell into a cell with hepatocyte-like properties. The iHeps induced according to the methods disclosed herein are functional induced hepatocytes (iHeps) in that they express I and II drug-metabolizing enzymes and phase III drug transporters and show superior drug metabolizing activity compared to iHeps obtained by prior art methods. The iHeps thus provide a cell resource for pharmaceutical applications.Type: GrantFiled: February 4, 2015Date of Patent: March 28, 2023Assignees: BeiHao Stem Cell and Regenerative Medicine Translational Research Institute, Peking University, Beijing Vitalstar Biotechnology Co., Ltd.Inventors: Hongkui Deng, Yuanyuan Du, Yan Shi, Jun Jia, Jinlin Wang, Chengang Xiang, Nan Song, Jun Xu, Ming Yin
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Patent number: 11602134Abstract: A preparation method of an anti-PD-1/PD-L1 monoclonal antibody (mAb)-induced autoimmune myocarditis model is provided, including: mediating a model with adeno-associated virus 9 (AAV9) to achieve the high expression of PDL1 in a myocardial tissue, and applying an anti-PD-1/PD-L1 mAb to the model with high PDL1 expression in the myocardial tissue for modeling. The present disclosure also provides use of an animal model prepared by the preparation method. The model prepared by the present disclosure truly simulates the pathogenesis and clinical course of autoimmune myocarditis in a patient administered with an anti-PD1/PD-L1 mAb, is close to a pathophysiological status of a clinical patient, has a high modeling rate, and can be dynamically monitored.Type: GrantFiled: January 10, 2022Date of Patent: March 14, 2023Assignee: PEKING UNION MEDICAL COLLEGE HOSPITALInventors: Yining Wang, Chanjuan Qu, Jian Wang, Yanyu Li, Kang Zhou, Jian Cao, Lu Lin, Xiao Li, Zhengyu Jin
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Patent number: 11591622Abstract: Disclosed herein are methods and compositions for targeted, nuclease-mediated insertion of transgene sequences into the genome of a cell.Type: GrantFiled: August 5, 2019Date of Patent: February 28, 2023Assignee: Sangamo Therapeutics, Inc.Inventors: Michael C. Holmes, Thomas Wechsler
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Patent number: 11589562Abstract: This disclosure relates to genetically modified rodent animals and rodent models of human diseases. More specifically, this disclosure relates to genetically modified rodents whose genome comprises a humanized Il1rl2 gene (coding for the IL1rl2 subunit of the IL-36R protein) and human IL-36?, ? and ? ligand genes. The genetically modified rodents disclosed herein display enhanced skin and intestinal inflammation as a preclinical model of psoriasis and IBD, respectively, and serve as a rodent model of human DITRA disease.Type: GrantFiled: July 16, 2019Date of Patent: February 28, 2023Assignee: Regeneran Pharmaceuticals, Inc.Inventors: Andrew J. Murphy, Alexander O. Mujica, Ka-Man Venus Lai, Sokol Haxhinasto
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Patent number: 11582956Abstract: Disclosed herein is a recombinant adenovirus genome, said adenovirus genome comprising a heterologous nucleic acid inserted into a cloning site of said genome, said heterologous nucleic acid comprising: (a) a first nucleic acid sequence comprising an adenovirus tripartite sequence (e.g., SEQ ID NO:1) operably linked to a second nucleic acid sequence encoding an interferon (e.g., SEQ ID NO:2); (b) a third nucleic acid sequence comprising a bovine growth hormone polyA termination sequence operably linked to said second nucleic acid sequence (e.g., SEQ ID NO:3); (c) a fourth nucleic acid sequence comprising a porcine elongation factor 1-alpha (EF1?) promoter (e.g., SEQ ID NO:4); (d) a fifth nucleic acid sequence operably linked to said fourth nucleic acid sequence, said fifth nucleic acid sequence encoding a suppressor of cytokine signaling 1 (SOCS1) protein (e.g., SEQ ID NO:5). Furthermore, there is disclosed a method of producing interferon in an animal (e.g., swine).Type: GrantFiled: September 3, 2019Date of Patent: February 21, 2023Assignee: The United States of America, as represented by The Secretary of AgricultureInventors: James J. Zhu, Elizabeth A. Bishop, Palaniappan Ramanathan
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Patent number: 11576984Abstract: Provided herein are methods and compositions related to the in vivo testing of therapeutic agents comprising a human Fc in genetically modified rodents (e.g., the testing of the pharmacokinetic and/or pharmacodynamic properties of such a therapeutic agent in genetically modified rodents). In some embodiments the genetically modified rodents express antibodies comprising a human Fc (e.g., a human IgG1 Fc, a human IgG4 Fc). In some embodiments, the rodents express fully human antibodies (i.e., antibodies having human heavy chains and human light (? or ?) chains). In certain embodiments the genetically modified rodents comprise one or more Fc receptors with a human extracellular domain (e.g., a Neonatal Fc Receptor (FcRn), a ?-2-microglobulin polypeptide (?2M), a Fc ? receptor 1? (Fc?R1?), a Fc ? receptor 1 alpha (Fc?R1a), a Fc gamma receptor 2a (Fc?R2a), a Fc gamma receptor 2b (Fc?R2b), a Fc gamma receptor 3a (Fc?R3a), a Fc gamma receptor 3b (Fc?R3b), a Fc gamma receptor 2c (Fc?R2c)).Type: GrantFiled: March 25, 2019Date of Patent: February 14, 2023Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Vera Voronina, Corey Momont, John McWhirter, Naxin Tu, Lynn MacDonald, Andrew J. Murphy
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Patent number: 11559551Abstract: Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins.Type: GrantFiled: April 5, 2021Date of Patent: January 24, 2023Assignee: VOR BIOPHARMA INC.Inventors: Joseph Bolen, Aleksandar Filip Radovic-Moreno, John Lydeard
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Patent number: 11535850Abstract: The present disclosure relates methods and compositions useful for prevention of porcine reproductive and respiratory syndrome virus (PRRSv) in animals, including animals of the species Sus scrofa. The present teachings relate to swine wherein at least one allele of a CD163 gene has been inactivated, and to specific methods and nucleic acid sequences used in gene editing to inactivate the CD163 gene. Swine wherein both alleles of the CD163 gene are inactivated are resistant to porcine reproductive and respiratory syndrome virus (PRRSv). Elite lines comprising homozygous CD163 edited genes retain their superior properties.Type: GrantFiled: January 21, 2022Date of Patent: December 27, 2022Assignee: Genus PLCInventors: Andrew Mark Cigan, Jonathan Edward Lightner, Matthew Scott Culbertson, William Thomas Christianson, Benjamin Beaton, Brian Burger, Dylan Barnes, Matthew Campbell
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Patent number: 11530388Abstract: Methods are disclosed herein for producing human hepatocytes from human induced pluripotent stem cells. Also provided are transgenic rats for the expansion of human hepatocytes, such as those produced using the methods disclosed herein.Type: GrantFiled: February 13, 2018Date of Patent: December 20, 2022Assignee: University of Pittsburgh—Of the Commonwealth System of Higher EducationInventors: Alejandro Soto-Gutierrez, Tomoji Mashimo, Alexandra Sylvie Collin de l'Hortet, Eduardo Cervantes Alvarez, Jorge Guzman Lepe, Kan Handa, Kazuki Takeishi, Yang Wang, Branimir Popovic
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Patent number: 11529393Abstract: Provided are compositions and methods for production of anti-inflammatory cytokines, growth factors, or chemokines. Provided are nucleic acids (e.g., expression vectors) that include an NF?B inflammation response element operably linked to a nucleotide sequence encoding an anti-inflammatory cytokine (e.g., IL-4). In some cases, the nucleic acid is an expression vector selected from: a linear expression vector, a circular expression vector, a plasmid, and a viral expression vector. Also provided are cells (e.g., mesenchymal stem cells—MSCs) comprising a nucleic acid that includes an NF?B inflammation response element operably linked to a nucleotide sequence encoding an anti-inflammatory cytokine. In some cases, the nucleic acid is integrated into the cell's genome.Type: GrantFiled: October 6, 2017Date of Patent: December 20, 2022Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Tzuhua Lin, Jukka Pajarinen, Stuart B. Goodman
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Patent number: 11529417Abstract: Compositions and methods are provided for improved wound healing. In particular, provided herein are compositions and methods for the direct delivery of Sirtuin-1 (Sirt1) or vectors encoding Sirt1 to the wounds (e.g., of diabetic patients).Type: GrantFiled: May 13, 2020Date of Patent: December 20, 2022Assignee: Northwestern UniversityInventors: Guillermo A. Ameer, Michele Jen, Jian Yang
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Patent number: 11528895Abstract: The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.Type: GrantFiled: July 14, 2015Date of Patent: December 20, 2022Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Andrew J. Murphy, John McWhirter, Naxin Tu, Vera Voronina, Cagan Gurer, Karolina Meagher, Sean Stevens
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Patent number: 11519005Abstract: The present disclosure provides a promoter having at least the core components of a duck retinoic acid-inducible gene I (RIG-I) promoter, as well as expression constructs having the duck RIG-I promoter operably linked to a gene product-encoding nucleic acid (e.g., an avian RIG-I protein), and recombinant host cells containing the duck RIG-I promoter, e.g., in such expression constructs. The present disclosure also provide animals genetically modified to have a gene encoding a duck RIG-I promoter operably linked to a gene product-encoding nucleic acid (e.g., an avian RIG-I protein, such as a duck RIG-I protein).Type: GrantFiled: September 26, 2018Date of Patent: December 6, 2022Inventors: Katharine Magor, Yanna Xiao
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Patent number: 11499138Abstract: Provided is a method for efficiently manufacturing high-purity peripheral nerve cells from undifferentiated cells. The method for manufacturing peripheral nerve cells from undifferentiated cells having an ability to differentiate into peripheral nerve cells includes the following steps (a) and (b): (a) culturing undifferentiated cells having an ability to differentiate into peripheral nerve cells to induce differentiation into neural progenitor cells without detaching a grown colony from a culture vessel; and (b) detaching the neural progenitor cells produced in the step (a) from the culture vessel, then seeding the cells at a seeding density of 2×105 to 6×105 cells/cm2 to a culture vessel, and culturing the cells for 14 to 42 days.Type: GrantFiled: October 20, 2017Date of Patent: November 15, 2022Assignees: NATIONAL UNIVERSITY CORPORATION GUNMA UNIVERSITY, KABUSHIKI KAISHA YAKULT HONSHAInventors: Masahiko Nishiyama, Susumu Rokudai, Shinji Yoshiyama, Hiroyuki Takahashi
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Patent number: 11459570Abstract: Methods for treating, and for identifying novel treatments for, neurodegenerative diseases, as well as animal and cellular models.Type: GrantFiled: June 14, 2019Date of Patent: October 4, 2022Assignee: The General Hospital CorporationInventors: Mark William Albers, Steven Rodriguez
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Patent number: 11447797Abstract: The invention provides an adeno-associated viral (AAV) vector comprising a capsid comprising the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 9, wherein the AAV vector further comprises a heterologous nucleic acid sequence, and wherein the heterologous nucleic acid sequence can encode the NGF-PTH fusion polypeptide or methylmalonyl CoA mutase enzyme. The invention also provides a polypeptide comprising nerve growth factor (NGF) signal peptide and parathyroid hormone (PTH), wherein the polypeptide can comprise, consist essentially of, or consist of the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 2. The invention provides a nucleic acid encoding the polypeptide, a vector comprising the nucleic acid, and a composition comprising the polypeptide, nucleic acid, or vector, as well as treatment methods comprising the polypeptide, nucleic acid, vector, or composition.Type: GrantFiled: May 12, 2016Date of Patent: September 20, 2022Assignee: The United States of America,as represented by the Secretary, Department of Health and Human ServiceInventors: John A. Chiorini, Giovanni Di Pasquale, Randy Chandler, Charles P. Venditti
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Patent number: 11427805Abstract: Disclosed herein are cell cultures comprising dorsal and/or ventral PDX1-positive foregut endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified dorsal and/or ventral PDX1-positive foregut endoderm cells as well as methods for enriching, isolating and purifying dorsal and/or ventral PDX1-positive foregut endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of dorsal and/or ventral PDX1-positive foregut endoderm cells, are also disclosed.Type: GrantFiled: November 26, 2018Date of Patent: August 30, 2022Assignee: ViaCyte, Inc.Inventors: Kevin Allen D'Amour, Alan D. Agulnick, Susan Eliazer, Emmanuel E. Baetge
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Patent number: 11419320Abstract: Disclosed is a cold-resistant and lean-type transgenic pig and a preparation method therefor, which relate to the field of genetic engineering. By transferring a mouse uncoupling protein 1 gene into the genome of a pig, a transgenic pig is obtained which can not only resist the cold but also have an increased lean meat rate by reducing fat deposition. Simultaneous improvement of two important production traits of pigs through the site-directed single gene manipulation not only lays a foundation for the application and basic research of genetic editing for big animals, but also provides with breading researchers a new way of thinking for improving traits of livestock.Type: GrantFiled: December 29, 2017Date of Patent: August 23, 2022Assignee: INSTITUTE OF ZOOLOGY, CHINESE ACADEMY OF SCIENCESInventors: Jianguo Zhao, Qiantao Zheng, Guosong Qin, Jing Yao, Chunwei Cao
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Patent number: 11419319Abstract: A genetically modified rodent is provided that comprises a modified Acvr1 gene that comprises a conditional altered exon 7 encoding R258G in anti sense orientation, flanked by site-specific recombinase recognition sites, wherein the altered exon is inverted to sense orientation upon action of a recombinase, resulting in ectopic bone formation.Type: GrantFiled: June 12, 2019Date of Patent: August 23, 2022Assignee: Regeneran Pharmaceuticals, Inc.Inventors: Sarah J. Hatsell, Aris N. Economides, Christopher Schoenherr, Vincent J. Idone