Involving Site-specific Recombination (e.g., Cre-lox, Etc.) Patents (Class 435/462)
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Patent number: 11912985Abstract: The present disclosure provides systems, compositions, and methods for simultaneously editing both strands of a double-stranded DNA sequence at a target site to be edited. Further provided herein are pharmaceutical compositions, polynucleotides, vectors, cells, and kits for simultaneously editing both strands of a double-stranded DNA sequence.Type: GrantFiled: November 7, 2022Date of Patent: February 27, 2024Assignees: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, Jonathan Ma Levy, Xin Gao, Christopher J. Podracky
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Patent number: 11845933Abstract: The disclosure relates to compositions comprising and methods for chemical modification of single guide RNA (sgRNA), tracrRNA and/or crRNA used individually or in combination with one another or Cas system components. Compositions comprising modified ribonucleic acids have been designed with chemical modification for even higher efficiency as unmodified native strand of sgRNA. Administration of modified ribonucleic acids will allow decreased immune response when administered to a subject, increased stability, increased editing efficiency and facilitated in vivo delivery of sgRNA via various delivery platforms. The disclosure also relates to methods of decreasing off-target effect of CRISPR and a CRISPR complex.Type: GrantFiled: February 3, 2017Date of Patent: December 19, 2023Assignee: Massachusetts Institute of TechnologyInventors: Hao Yin, Daniel G. Anderson, Robert S. Langer
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Patent number: 11738047Abstract: The present disclosure provides modified immune cell (e.g., modified T cell) comprising an exogenous T cell receptor (TCR) having specificity for NY-ESO-1. The present disclosure provides modified immune cells or precursors thereof (e.g., modified T cells) comprising an exogenous TCR and a switch receptor. Gene edited modified cells are also provided, such that the expression of one or more of an endogenous T-cell receptor gene (e.g., TRAC, TRBC) or an endogenous immune checkpoint gene (e.g., PD-1 or TIM-3) is downregulated.Type: GrantFiled: December 11, 2018Date of Patent: August 29, 2023Assignee: The Trustees of the University of PennsylvaniaInventors: Yangbing Zhao, Xiaojun Liu
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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: 11578323Abstract: Aspects of this invention inter alia relate to novel systems for targeting, editing or manipulating DNA in a cell, comprising one or more heterologous vector(s) encoding a SluCas9 nuclease from Staphylococcus lugdunensis or variants thereof, and one or more guide RNAs (gRNAs), or a SluCas9 nuclease or variant thereof and one or more gRNAs.Type: GrantFiled: December 14, 2018Date of Patent: February 14, 2023Assignees: BAYER HEALTHCARE LLC, CRISPR THERAPEUTICS AGInventors: Andre Cohnen, Moritz Schmidt, Wayne Coco, Ashish Gupta, Jan Tebbe, Cindy Schulenburg, Christian Pitzler, Michael Biag Gamalinda, Sabine Jach, Florian Richter, Anup Arumughan, Corinna Saalwächter
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Patent number: 11530272Abstract: RNA Control Devices and/or destabilizing elements (DE) can regulate the expression of Chimeric Antigen Receptors (CARs) in eukaryotic cells. More specifically, DEs, RNA Control Devices, and/or side-CARs can be used with small molecule ligands to regulate the expression of Chimeric Antigen Receptors. These DE-CARs, Smart CARs (Smart=small molecule actuatable RNA trigger), Smart-DE-CARs, and/or Side-CARs can be used in the treatment of disease.Type: GrantFiled: December 21, 2017Date of Patent: December 20, 2022Assignee: Chimera Bioengineering, Inc.Inventors: Benjamin Wang, Gusti Zeiner
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Patent number: 11401522Abstract: Compositions and methods are provided for genome modification at a target site in the genome of a fungal cell. The methods and compositions are drawn to a guide polynucleotide/Cas endonuclease system for promoting modification of the DNA sequence at a target site in a fungal host cell genome.Type: GrantFiled: December 16, 2015Date of Patent: August 2, 2022Assignee: DANISCO US INCInventors: Benjamin S. Bower, Jimmy Chan, Jing Ge, Xiaogang Gu, Susan Mampusti Madrid, Danfeng Song, Mingmin Song, Michael Ward, Steven Sungin Kim
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Patent number: 11147837Abstract: 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: GrantFiled: September 2, 2016Date of Patent: October 19, 2021Assignees: Regents of the University of Minnesota, Intima Bioscience, Inc., The United States of America, as Represented by the Secretary, Department of Health and Human ServicesInventors: Branden Moriarity, Beau Webber, Modassir Choudhry, R. Scott McIvor, David Largaespada, Steven A. Rosenberg, Douglas C. Palmer, Nicholas P. Restifo
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Patent number: 11060083Abstract: The present invention provides a method and compositions utilizing the CRISPR system to disrupt a target gene in eukaryotic cells to produce double allele knock outs. The method finds use in producing afucosylated antibodies with enhanced ADCC activity.Type: GrantFiled: May 19, 2017Date of Patent: July 13, 2021Assignee: Larix Bioscience LLCInventors: Bo Yu, James Larrick
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Patent number: 11020430Abstract: This disclosure relates to the genetic modification of DNMT3A gene in immune cells. In certain embodiments, the modified immune cells may be used in adoptive T cells therapies to enhance immune responses against cancer or chronic infections. In certain embodiments, the disclosure relates to deleting, changing, or inserting nucleotides within the DNMT3A gene in immune cells, e.g., human CD8 T cells, such that the DNMT3A gene product does not function for methylation. In certain embodiments, modification of the DNMT3A gene provides an improvement in antigen-specific T cells functions and/or an enhancement of the longevity of the cells.Type: GrantFiled: November 4, 2016Date of Patent: June 1, 2021Assignees: Emory University, St. Jude Children's Research Hospital, Inc.Inventors: Rafi Ahmed, Benjamin Youngblood
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Patent number: 11001829Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems.Type: GrantFiled: March 24, 2017Date of Patent: May 11, 2021Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Feng Zhang, Silvana Konermann, Mark D. Brigham, Alexandra Trevino
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Patent number: 10858639Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain or a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: GrantFiled: September 5, 2014Date of Patent: December 8, 2020Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Patent number: 10787654Abstract: The present invention is directed to methods and compositions for genome editing and DNA targeting of proteins.Type: GrantFiled: January 23, 2015Date of Patent: September 29, 2020Assignee: NORTH CAROLINA STATE UNIVERSITYInventors: Rodolphe Barrangou, Kurt M. Selle, Alexandra E. Briner
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Patent number: 10745714Abstract: Disclosed herein are Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) 9-based system related compositions and methods of using said CRISPR/Cas9-based system related compositions for altering gene expression and genome engineering. Also disclosed herein are compositions and methods of using said compositions for altering gene expression and genome engineering in muscle, such as skeletal muscle and cardiac muscle.Type: GrantFiled: May 29, 2018Date of Patent: August 18, 2020Assignee: Duke UniversityInventors: Charles A. Gersbach, Isaac B. Hilton, Pablo Perez-Pinera, Ami M. Kabadi, Pratiksha I. Thakore, David G. Ousterout, Joshua B. Black
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Patent number: 10711285Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity.Type: GrantFiled: December 17, 2015Date of Patent: July 14, 2020Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Feng Zhang, Patrick Hsu, Chie-yu Lin, Fei Ran
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Patent number: 10701911Abstract: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/BIN, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ (NSG), NOD.Cg-Rag1tm1Mom IL2rgtm1Wjl/SzJ (NRG) and NOD.Cg-Prkdcscid IL2rgtm1Sug/JicTAc (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice.Type: GrantFiled: June 16, 2016Date of Patent: July 7, 2020Assignees: The Jackson Laboratory, University of MassachusettsInventors: Leonard D. Shultz, Mohit Kumar Verma, Dale L. Greiner, Michael A. Brehm
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Patent number: 10550372Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems.Type: GrantFiled: June 10, 2016Date of Patent: February 4, 2020Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, University of Tokyo, President and Fellows of Harvard CollegeInventors: Silvana Konermann, Alexandro Trevino, Mark Brigham, Fei Ran, Patrick Hsu, Chie-yu Lin, Osamu Nureki, Hiroshi Nishimasu, Ryuichiro Ishitani, Feng Zhang
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Patent number: 10531648Abstract: A genetically modified mouse is provided that comprises a conditional Acvr1 allele that comprises a mutated exon that, upon induction, converts to a mutant exon phenotype, wherein the mutant exon phenotype includes ectopic bone formation. Mice comprising a mutant Acvr1 exon 5 in antisense orientation, flanked by site-specific recombinase recognition sites, are provided, wherein the mice further comprise a site-specific recombinase that recognizes the site-specific recombinase recognitions sites, wherein the recombinase is induced upon exposure of the mouse to tamoxifen. Upon exposure to tamoxifen, the recombinase is expressed and acts on the RRS-flanked mutant exon 5 and places the mutant exon 5 in sense orientation and deletes the wild-type exon.Type: GrantFiled: October 30, 2018Date of Patent: January 14, 2020Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Aris N. Economides, Sarah Jane Hatsell
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Patent number: 10525082Abstract: Disclosed are methods of making a genetically modified immune cell for modifying a tumor microenvironment (TME) and methods of modifying a tumor microenvironment (TME). In some embodiments, the method can include delivering a first vector to an immune cell, wherein the first vector comprises a nucleic acid encoding a protein that induces T-cell proliferation, promotes persistence and activation of endogenous or adoptively transferred NK or T cells and/or induces production of an interleukin, an interferon, a PD-1 checkpoint binding protein, HMGB1, MyD88, a cytokine or a chemokine. Methods of modulating the suppression of the immune response in a tumor microenvironment, minimizing the proliferation of tumor and suppressive cells, and increasing the efficiency of an anti-cancer therapy, anti-infection therapy, antibacterial therapy, anti-viral therapy, or anti-tumoral therapy are also provided.Type: GrantFiled: September 7, 2016Date of Patent: January 7, 2020Assignee: Seattle Children's HospitalInventors: Courtney Crane, Michael Jensen, Kara White Moyes, Nicole Lieberman
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Patent number: 10519454Abstract: The disclosure provided herewith relates to a Campylobacter jejuni CRISPR/CAS system-derived RGEN and a use thereof.Type: GrantFiled: January 31, 2017Date of Patent: December 31, 2019Assignee: TOOLGEN INCORPORATEDInventors: Eun Ji Kim, Seok Joong Kim
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Patent number: 10508152Abstract: The present invention relates generally to the field of RNA Control Devices and/or destabilizing elements (DE) combined with Chimeric Antigen Receptors (CARs) in eukaryotic cells. The present invention also relates to split CARs (Side-CARs) in eukaryotic cells. More specifically, the present invention relates to DEs, RNA Control Devices, and/or side-CARs combined with Chimeric Antigen Receptors to make small molecule actuatable CAR polypeptides. The present invention also relates to DE-CARs, Smart CARs (Smart=small molecule actuatable RNA trigger), Smart-DE-CARs, and/or Side-CARs for use in the treatment of disease.Type: GrantFiled: September 18, 2017Date of Patent: December 17, 2019Assignee: Chimera Bioengineering, Inc.Inventors: Benjamin Wang, Gusti Zeiner
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Patent number: 10470444Abstract: A genetically modified mouse is provided that comprises a conditional Acvr1 allele that comprises a mutated exon that, upon induction, converts to a mutant exon phenotype, wherein the mutant exon phenotype includes ectopic bone formation. Mice comprising a mutant Acvr1 exon 5 in antisense orientation, flanked by site-specific recombinase recognition sites, are provided, wherein the mice further comprise a site-specific recombinase that recognizes the site-specific recombinase recognitions sites, wherein the recombinase is induced upon exposure of the mouse to tamoxifen. Upon exposure to tamoxifen, the recombinase is expressed and acts on the RRS-flanked mutant exon 5 and places the mutant exon 5 in sense orientation and deletes the wild-type exon.Type: GrantFiled: October 30, 2018Date of Patent: November 12, 2019Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Aris N. Economides, Sarah Jane Hatsell
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Patent number: 10448621Abstract: A genetically modified mouse is provided that comprises a conditional Acvr1 allele that comprises a mutated exon that, upon induction, converts to a mutant exon phenotype, wherein the mutant exon phenotype includes ectopic bone formation. Mice comprising a mutant Acvr1 exon 5 in antisense orientation, flanked by site-specific recombinase recognition sites, are provided, wherein the mice further comprise a site-specific recombinase that recognizes the site-specific recombinase recognitions sites, wherein the recombinase is induced upon exposure of the mouse to tamoxifen. Upon exposure to tamoxifen, the recombinase is expressed and acts on the RRS-flanked mutant exon 5 and places the mutant exon 5 in sense orientation and deletes the wild-type exon.Type: GrantFiled: May 18, 2018Date of Patent: October 22, 2019Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Aris N. Economides, Sarah Jane Hatsell
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Patent number: 10435699Abstract: Compositions and methods are provided for stacking multiple independent transgenic loci into the genome of a plant. Compositions include plants, seeds or plant cells comprising at least one transgenic target site and at least one genomic locus of interest integrated at different genomic sites within a genomic window. Plant breeding techniques can be employed such that the transgenic target site and the genomic locus of interest can be bred together. In this way, multiple independent transgene integrations can be generated within a genomic window to create a complex trait locus. The complex trait locus is designed such that the transgenic target sites and/or genomic loci of interest can segregate independently of each other, thus providing the benefit of altering a complex trait locus by breeding-in and breeding-away specific elements. Various methods can also be employed to modify the target sites such that they contain a variety of polynucleotides of interest.Type: GrantFiled: January 24, 2013Date of Patent: October 8, 2019Assignees: E I DU PONT DE NEMOURS AND COMPANY, PIONEER HI-BRED INTERNATIONAL, INC.Inventors: Saverio Carl Falco, Michael W Lassner, Zhongsen Li, Christopher Jay Scelonge
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Patent number: 10392633Abstract: Nucleic acid constructs and methods for rendering modifications to a genome are provided, wherein the modifications comprise null alleles, conditional alleles and null alleles comprising COINs. Multifunctional alleles (MFA) are provided, as well as methods for making them, which afford the ability in a single targeting to introduce an allele that can be used to generate a null allele, a conditional allele, or an allele that is a null allele and that further includes a COIN. MFAs comprise pairs of cognate recombinase recognition sites, an actuating sequence and/or a drug selection cassette, and a nucleotide sequence of interest, and a COIN, wherein upon action of a recombinase a conditional allele with a COIN is formed. In a further embodiment, action of a second recombinase forms an allele that contains only a COIN in sense orientation. In a further embodiment, action by a third recombinase forms an allele that contains only the actuating sequence in sense orientation.Type: GrantFiled: July 12, 2013Date of Patent: August 27, 2019Assignee: REGENERON PHARMACEUTICALS, INC.Inventors: Aris N. Economides, Andrew J. Murphy, Peter Matthew Lengyel, Peter H. A. Yang
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Patent number: 10323073Abstract: Methods and products (e.g., gRNAs, recombinant fusion proteins, frataxin targeting systems, compositions and kits) are described for increasing frataxin expression/levels in a cell, as well as uses of such methods and products, for example for the treatment of Friedreich ataxia in a subject suffering therefrom.Type: GrantFiled: March 20, 2015Date of Patent: June 18, 2019Assignee: UNIVERSITÉ LAVALInventors: Jacques P. Tremblay, Pierre Chapdelaine, Joël Rousseau
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Patent number: 10081817Abstract: The present invention provides a method for obtaining site-specific recombination in a eukaryotic cell, the method comprising providing a eukaryotic cell that comprises a first recombination attachment site and a second recombination attachment site; contacting the first and second recombination attachment sites with a prokaryotic recombinase polypeptide, resulting in recombination between the recombination attachment sites, wherein the recombinase polypeptide can mediate recombination between the first and second recombination attachment sites, the first recombination attachment site is a phage genomic recombination attachment site (attP) or a bacterial genomic recombination attachment site (attB), the second recombination site is attB or attP, and the recombinase is selected from the group consisting of a Listeria monocytogenes phage recombinase, a Streptococcus pyogenes phage recombinase, a Bacillus subtilis phage recombinase, a Mycobacterium tuberculosis phage recombinase and a Mycobacterium smegmatis phaType: GrantFiled: October 31, 2016Date of Patent: September 25, 2018Assignee: Intrexon CorporationInventor: Malla Padidam
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Patent number: 10030245Abstract: Methods for producing in a plant a complex transgenic trait locus comprising at least two altered target sequences in a genomic region of interest are disclosed. The methods involve the use of two or more double-strand-break-inducing agents, each of which can cause a double-strand break in a target sequence in the genomic region of interest which results in an alteration in the target sequence. Also disclosed are complex transgenic trait loci in plants. A complex transgenic trait locus comprises at least two altered target sequences that are genetically linked to a polynucleotide of interest. Plants, plant cells, plant parts, and seeds comprising one or more complex transgenic trait loci are also disclosed.Type: GrantFiled: March 22, 2012Date of Patent: July 24, 2018Assignees: E I DU PONT DE NEMOURS AND COMPANY, PIONEER HI-BRED INTERNATIONAL, INC.Inventors: Michael Lassner, Derek Jantz, James Jefferson Smith, Mark Cigan, Carl Falco, Huirong Gao, Zhongsen Li, Zhan-Bin Liu, Sergei Svitashev
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Patent number: 9777064Abstract: The present invention relates generally to the field of RNA Control Devices and/or destabilizing elements (DE) combined with Chimeric Antigen Receptors (CARs) in eukaryotic cells. The present invention also relates to split CARs (Side-CARs) in eukaryotic cells. More specifically, the present invention relates to DEs, RNA Control Devices, and/or side-CARs combined with Chimeric Antigen Receptors to make small molecule actuatable CAR polypeptides. The present invention also relates to DE-CARs, Smart CARs (Smart=small molecule actuatable RNA trigger), Smart-DE-CARs, and/or Side-CARs for use in the treatment of disease.Type: GrantFiled: March 15, 2016Date of Patent: October 3, 2017Assignee: Chimera Bioengineering, Inc.Inventors: Benjamin Wang, Gusti Zeiner
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Patent number: 9572837Abstract: The present disclosure relates to compositions and methods for reducing immune tolerance associated with CAR T cell therapy. Embodiments of the present disclosure include isolated nucleic acid sequence comprising a nucleic acid sequence that encodes modified programmed cell death protein 1 (PD-1) and a nucleic acid sequence that encodes chimeric antigen receptor (CAR).Type: GrantFiled: April 7, 2016Date of Patent: February 21, 2017Assignee: Innovative Cellular Therapeutics CO., LTD.Inventor: Zhao Wu
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Patent number: 9510569Abstract: A genetically modified mouse is provided that comprises a conditional Acvr1 allele that comprises a mutated exon that, upon induction, converts to a mutant exon phenotype, wherein the mutant exon phenotype includes ectopic bone formation. Mice comprising a mutant Acvr1 exon 5 in antisense orientation, flanked by site-specific recombinase recognition sites, are provided, wherein the mice further comprise a site-specific recombinase that recognizes the site-specific recombinase recognitions sites, wherein the recombinase is induced upon exposure of the mouse to tamoxifen. Upon exposure to tamoxifen, the recombinase is expressed and acts on the RRS-flanked mutant exon 5 and places the mutant exon 5 in sense orientation and deletes the wild-type exon.Type: GrantFiled: March 12, 2014Date of Patent: December 6, 2016Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Aris N. Economides, Sarah Jane Hatsell
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Patent number: 9222105Abstract: Nucleases and methods of using these nucleases for modification of an HPRT locus and for increasing the frequency of gene modification at a targeted locus and clones and for generating animals.Type: GrantFiled: October 25, 2012Date of Patent: December 29, 2015Assignees: Sangamo BioSciences, Inc., The Regents of the University of CaliforniaInventors: Gregory J. Cost, Michael C. Holmes, Noriyuki Kasahara, Josee Laganiere, Jeffrey C. Miller, David Paschon, Edward J. Rebar, Fyodor Urnov, Lei Zhang
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Patent number: 9163232Abstract: The invention relates to a method for manufacturing a recombinant polyclonal protein composition, in particular a recombinant polyclonal antibody composition. The method comprises obtaining a collection of cells transfected with a library of variant nucleic acid sequences, wherein each call in the collection is transfected with and capable of expressing one member of the library, which encodes a distinct member of a polyclonal protein that binds a particular antigen and which is located at the same single site in the genome of individual cells in said collection, wherein said nucleic acid sequence is not naturally associated with said cell in the collection. The cells are cultured under suitable conditions for expression of the polyclonal protein, which is obtained from the cells or culture supernatant. The present method is suitable for manufacturing recombinant polyclonal antibodies, thereby making available a superior replacement of plasma-derived therapeutic immunoglobulin products.Type: GrantFiled: December 19, 2008Date of Patent: October 20, 2015Assignee: Symphogen A/SInventors: John S. Haurum, Finn C. Wiberg, Vincent W. Coljee, Jacqueline Sharon, Chiou-Ying Yang
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Publication number: 20150140664Abstract: Methods of simultaneously excising large nucleic acid sequences from a target nucleic acid and inserting large foreign nucleic sequences into the target nucleic acid sequence using DNA binding protein nucleases are described.Type: ApplicationFiled: June 30, 2014Publication date: May 21, 2015Inventors: Susan M. BYRNE, George M. CHURCH
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Publication number: 20150140665Abstract: Methods for inserting a polynucleotide sequence into the genome of a human cell are provided. The present methods result in insertion of a polynucleotide sequence of interest into the H11 locus in the genome of a human cell. Also provided are nucleic acids that include sequences for integrating a polynucleotide sequence of interest into the H11 locus in the genome of a human cell. A transgenic human cell including site specific recombination sites at the H11 locus is also disclosed.Type: ApplicationFiled: November 12, 2014Publication date: May 21, 2015Inventors: Michele Pamela Calos, Ruby Yanru Tsai, Fangfang Zhu, Matthew Gamboa, Alfonso P. Farruggio, Simon Hippenmeyer, Bosiljka Tasic, Birgitt Schüle
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Patent number: 9034650Abstract: The present invention provides a method for obtaining site-specific recombination in a eukaryotic cell, the method comprising providing a eukaryotic cell that comprises a first recombination attachment site and a second recombination attachment site; contacting the first and second recombination attachment sites with a prokaryotic recombinase polypeptide, resulting in recombination between the recombination attachment sites, wherein the recombinase polypeptide can mediate recombination between the first and second recombination attachment sites, the first recombination attachment site is a phage genomic recombination attachment site (attP) or a bacterial genomic recombination attachment site (attB), the second recombination site is attB or attP, and the recombinase is selected from the group consisting of a Listeria monocytogenes phage recombinase, a Streptococcus pyogenes phage recombinase, a Bacillus subtilis phage recombinase, a Mycobacterium tuberculosis phage recombinase and a Mycobacterium smegmatis phaType: GrantFiled: February 2, 2005Date of Patent: May 19, 2015Assignee: Intrexon CorporationInventor: Malla Padidam
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Publication number: 20150125958Abstract: Disclosed herein are methods for controlling stem cell differentiation through the introduction of transgenes having Xic, Tsix, or Xite sequences to block differentiation and the removal of the transgenes to allow differentiation. Also disclosed are small RNA molecules and methods for using the small RNA molecules to control stem cell differentiation. Also disclosed are stem cells genetically modified by the introduction of Xic, Tsix, or Xite sequences.Type: ApplicationFiled: October 6, 2014Publication date: May 7, 2015Inventor: JEANNIE T. LEE
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Publication number: 20150128300Abstract: The disclosure provides methods and compositions for generating conditional knock-out alleles using donor constructs together with sequence-specific nucleases to generate conditional knock-out alleles. Specifically, the donor construct comprises a 5? homology region, a 5? recombinase recognition site, a donor sequence, a 3? recombinase recognition site, and a 3? homology region. Further disclosed are the donor sequences each comprises a target sequence having at least one neutral mutation. Different sequence-specific nucleases can be used with the donor constructs are further disclosed.Type: ApplicationFiled: June 12, 2013Publication date: May 7, 2015Inventors: Soren Warming, Keith R. Anderson
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Publication number: 20150118755Abstract: The disclosure relates to a method of reprogramming one or more somatic cells, e.g., partially differentiated or fully/terminally differentiated somatic cells, to a less differentiated state, e.g., a pluripotent or multipotent state. In further embodiments the invention also relates to reprogrammed somatic cells produced by methods of the invention, to uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells.Type: ApplicationFiled: August 29, 2014Publication date: April 30, 2015Inventors: Rudolf Jaenisch, Yaqub Hanna, Marius Wernig, Christopher J. Lengner, Alexander Meissner, Oliver Tobias Brambrink, G. Grant Welstead, Ruth Foreman
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Publication number: 20150110762Abstract: The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a cell.Type: ApplicationFiled: October 16, 2014Publication date: April 23, 2015Inventors: Michael C. Holmes, Jianbin Wang
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Publication number: 20150079064Abstract: Disclosed herein are transcription activator-like effector nuclease (TALEN)-related compositions and methods of using said TALENs for correcting mutant genes.Type: ApplicationFiled: April 26, 2013Publication date: March 19, 2015Applicant: Duke UniversityInventors: Charles Gersbach, David Ousterout
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Publication number: 20150079681Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.Type: ApplicationFiled: October 24, 2014Publication date: March 19, 2015Inventor: Feng Zhang
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Publication number: 20150079680Abstract: The invention relates to an approach for introducing one or more desired insertions and/or deletions of known sizes into one or more predefined locations in a nucleic acid (eg, in a cell or organism genome). They developed techniques to do this either in a sequential fashion or by inserting a discrete DNA fragment of defined size into the genome precisely in a predefined location or carrying out a discrete deletion of a defined size at a precise location. The technique is based on the observation that DNA single-stranded breaks are preferentially repaired through the HDR pathway, and this reduces the chances of indels (eg, produced by NHEJ) in the present invention and thus is more efficient than prior art techniques. The invention also provides sequential insertion and/or deletions using single- or double-stranded DNA cutting.Type: ApplicationFiled: September 18, 2014Publication date: March 19, 2015Inventors: Allan Bradley, Hanif Ali, E-Chiang Lee
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Publication number: 20150072368Abstract: Novel transcription units that may be used in expression vectors. The transcription unit allow antibodies to be produced whose gain in productivity is not linked to a particular antigenic target antibody and therefore by extrapolation to a given recombinant protein, nor linked to the culture medium.Type: ApplicationFiled: February 8, 2013Publication date: March 12, 2015Applicant: LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIESInventors: Alexandre Fontayne, François Coutard
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Publication number: 20150071900Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases.Type: ApplicationFiled: July 8, 2014Publication date: March 12, 2015Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, Johnny Hao Hu
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Publication number: 20150071899Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific nucleic acid modification using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a nuclease catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: ApplicationFiled: June 30, 2014Publication date: March 12, 2015Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Publication number: 20150071898Abstract: Some aspects of this disclosure provide compositions, methods, and kits for improving the specificity of RNA-programmable endonucleases, such as Cas9. Also provided are variants of Cas9, e.g., Cas9 dimers and fusion proteins, engineered to have improved specificity for cleaving nucleic acid targets. Also provided are compositions, methods, and kits for site-specific recombination, using Cas9 fusion proteins (e.g., nuclease-inactivated Cas9 fused to a recombinase catalytic domain). Such Cas9 variants are useful in clinical and research settings involving site-specific modification of DNA, for example, genomic modifications.Type: ApplicationFiled: June 30, 2014Publication date: March 12, 2015Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, David B. Thompson
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Publication number: 20150071889Abstract: Disclosed herein are methods, compositions, and kits for high efficiency, site-specific genomic editing of cells.Type: ApplicationFiled: September 12, 2014Publication date: March 12, 2015Inventors: Kiran Musunuru, Chad A. Cowan, Derrick J. Rossi
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Publication number: 20150067898Abstract: Methods, uses, and animals for introgression of alleles between animals, including SNPs. One embodiment involves introducing a targeted targeting endonuclease system and a HDR template into a cell with a mismatch in the binding of the targeting endonuclease and the targeted site.Type: ApplicationFiled: April 28, 2014Publication date: March 5, 2015Inventors: Scott C. Fahrenkrug, Daniel F. Carlson
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Patent number: RE49121Abstract: A genetically modified mouse is provided that comprises a conditional Acvr1 allele that comprises a mutated exon that, upon induction, converts to a mutant exon phenotype, wherein the mutant exon phenotype includes ectopic bone formation. Mice comprising a mutant Acvr1 exon 5 in antisense orientation, flanked by site-specific recombinase recognition sites, are provided, wherein the mice further comprise a site-specific recombinase that recognizes the site-specific recombinase recognitions sites, wherein the recombinase is induced upon exposure of the mouse to tamoxifen. Upon exposure to tamoxifen, the recombinase is expressed and acts on the RRS-flanked mutant exon 5 and places the mutant exon 5 in sense orientation and deletes the wild-type exon.Type: GrantFiled: November 13, 2018Date of Patent: July 5, 2022Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Aris N. Economides, Sarah Jane Hatsell