Patents Assigned to SPARK THERAPEUTICS, INC.
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Publication number: 20240101972Abstract: The presently disclosed subject matter relates to compositions and methods for regulating recombinant adeno-associated virus (rAAV) production in cell culture. In particular, the presently disclosed subject matter relates to strategies to overcome AAV Rep protein-mediated cytotoxicity by reversible post-translational regulation of the expression of AAV Rep and helper proteins, resulting in regulated rAAV production.Type: ApplicationFiled: December 11, 2023Publication date: March 28, 2024Applicant: SPARK THERAPEUTICS, INC.Inventors: Mustafa Yazicioglu, Ahmet Yunus Ozdemir
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Publication number: 20230241247Abstract: Disclosed herein are methods for treating patients that may develop or already have pre-existing gene therapy neutralizing antibodies by administering an agent that blocks, inhibits or reduces the interaction between immunoglobulin G (IgG) and the neonatal Fc receptor (FcRn), such as an anti-FcRn antibody, to reduce IgG recycling and enhance IgG clearance in vivo. Also disclosed are methods for utilizing agents that reduce interaction of IgG with FcRn for gene therapy treatment of a disease in a patient in need thereof.Type: ApplicationFiled: January 22, 2021Publication date: August 3, 2023Applicant: SPARK THERAPEUTICS, INC.Inventor: Sean ARMOUR
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Patent number: 11702639Abstract: In accordance with the invention, provided herein are methods for purifying recombinant adeno-associated (rAAV) vector particles.Type: GrantFiled: March 31, 2017Date of Patent: July 18, 2023Assignee: SPARK THERAPEUTICS, INC.Inventors: Guang Qu, Younghoon Oh, Lin Lu, John Fraser Wright
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Publication number: 20230040275Abstract: Nucleic acids encoding fusion proteins that contain an unwanted antigen and a leader sequence for cell secretion are described. Also described are expression cassettes, vectors, cells, and cell lines containing the nucleic acids, as well as methods of using the nucleic acids to treat autoimmune, allergic and other diseases and disorders, such as multiple sclerosis.Type: ApplicationFiled: November 19, 2020Publication date: February 9, 2023Applicant: SPARK THERAPEUTICS, INC.Inventors: David William ANDERSON, Brittney L. GURDA, Federico MINGOZZI, Mustafa N. YAZICIOGLU, William QUINN
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Publication number: 20220387560Abstract: Disclosed herein are compositions and methods of treating and/or correcting ocular disease in a subject, such as a mammal (e.g., human) eye using an Adeno-associated virus (AAV) system. The AAV system employs a nucleic acid encoding a CRISPR-Cas9 system for targeted gene disruption or correction.Type: ApplicationFiled: July 29, 2022Publication date: December 8, 2022Applicant: SPARK THERAPEUTICS, INC.Inventors: George Buchlis, Xavier Anguela, Katherine A. High
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Publication number: 20220362408Abstract: The invention provides expression cassettes. In certain embodiments, an expression cassette comprises (a) a regulatory element at least 90% identical to the sequence of any of SEQ ID NOs:2-67, and (b) a nucleic acid sequence encoding a Factor VIII protein having a B domain deletion (FVIII-BDD), where the nucleic acid sequence of (a) is at least 90% identical to the sequence of SEQ ID NO:77, where the regulatory element is operably linked to the nucleic acid sequence, and where no intron is present between the regulatory element and the nucleic acid sequence encoding FVIII-BDD, or where no more than 0-107 nucleotides of untranslated nucleic acid is between the regulatory element and the nucleic acid sequence encoding FVIII-BDD. In certain embodiments, expression cassettes contain sequence elements having CpG(s) substituted with CpT, CpA, TpG, or ApG at the same position(s) or has CpG reduced nucleic acid sequences.Type: ApplicationFiled: August 23, 2019Publication date: November 17, 2022Applicant: SPARK THERAPEUTICS, INC.Inventors: Xavier ANGUELA, Liron ELKOUBY
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Publication number: 20220184188Abstract: Disclosed herein are methods for treating a primate in need of tripeptidyl peptidase 1 (TPP1), comprising (a) providing a recombinant adeno-associated virus (AAV) vector comprising a nucleic acid encoding TPP1; and (b) administering an amount of the recombinant AAV vector to the central nervous system (CNS) of the primate, wherein the TPP1 is expressed in the primate.Type: ApplicationFiled: January 31, 2020Publication date: June 16, 2022Applicant: SPARK THERAPEUTICS, INC.Inventors: David William ANDERSON, Maryann TOTO, Sue E.I. DASEN
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Publication number: 20220025396Abstract: Disclosed herein are packaging cell lines, in which adenovirus (Ad) E1A is constitutively expressed, that also contain integrated AAV rep and cap genes. The packaging cell lines exhibit little to no expressed Rep protein until helper virus function, such as adenovirus (Ad) E4, E2A and/or VA RNA are provided by, for example, transduction of the cells with a virus, vector or plasmid, such as an Ad-AAV hybrid virus. The promoter driving expression of AAV rep gene can be positioned far enough upstream (5?) of the rep coding sequence that E1A is unable to activate the promoter, activate substantial transcription of the rep gene and in turn produce Rep protein. Introduction of helper virus function, such as E2A, E4 and/or VA RNA into these packaging cells is able to drive AAV rep gene transcription, subsequent Rep protein expression and production of rAAV vector particles.Type: ApplicationFiled: May 7, 2019Publication date: January 27, 2022Applicant: Spark Therapeutics, Inc.Inventors: Guang QU, Denis PHICHITH, Jingmin ZHOU
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Publication number: 20220011308Abstract: Disclosed herein are methods for analyzing for or detecting the presence of non-antibody inhibitors and/or enhancers of adeno-associated virus (AAV) vector cell transduction in a biological sample from a subject. Also disclosed herein are methods for analyzing for, or detecting the presence of, AAV binding antibodies that inhibit, reduce or decrease AAV vector cell transduction in a biological sample from a subject. The methods rely, in part, on the use of empty capsid AAV particles to absorb AAV binding antibodies, to detect enhancers or inhibitors of AAV vector cell transduction, when present, in a biological sample analyzed for AAV neutralizing antibodies (NAbs).Type: ApplicationFiled: November 15, 2019Publication date: January 13, 2022Applicant: SPARK THERAPEUTICS, INC.Inventors: Klaudia KURANDA, Xavier ANGUELA, Federico MINGOZZI
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Publication number: 20210371877Abstract: A composition includes an adeno-associated vims (AAV) vector in a lipid nanoparticle (LNP). The AAV vector can include a heterologous nucleic acid sequence, optionally an inverted terminal repeat (ITR) positioned 5? of the heterologous nucleic acid sequence and an ITR positioned 3? of the heterologous nucleic acid sequence. The AAV vector can further include expression control elements (e.g., a promoter and/or enhancer), and intron, and/or or a polyadenylation signal.Type: ApplicationFiled: December 18, 2018Publication date: December 2, 2021Applicant: SPARK THERAPEUTICS, INC.Inventors: Andrew William SHAW, Xavier ANGUELA
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Publication number: 20210363192Abstract: The invention provides modified adeno-associated virus (AAV) capsid proteins. Modified AAV capsid proteins include, for example, capsid proteins modified to have a peptide insertion comprising a nuclear localization signal (NLS) sequence, capsid proteins modified to have an amino acid substitution at an RXXL site or a (L/P)PXY site, where X can be any amino acid, and capsid proteins modified to have one or more particular amino acid positions substituted with a different amino acid.Type: ApplicationFiled: April 26, 2019Publication date: November 25, 2021Applicant: SPARK THERAPEUTICS, INC.Inventors: Xavier ANGUELA, Sean ARMOUR, Nicholas KEISER, Suryanarayan SOMANATHAN, Mustafa N. YAZICIOGLU
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Publication number: 20210348210Abstract: Methods for assaying function and/or activity and/or potency of isomerohydrolase proteins are provided.Type: ApplicationFiled: April 28, 2017Publication date: November 11, 2021Applicant: SPARK THERAPEUTICS, INC.Inventor: Linda COUTO
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Patent number: 11168124Abstract: CpG reduced nucleic acid variants encoding FVIII protein and methods of use thereof are disclosed. In particular embodiments, CpG reduced nucleic acid variants encoding FVIII are expressed more efficiently by cells, are secreted at increased levels by cells over wild-type Factor VIII proteins, exhibit enhanced expression and/or activity over wild-type Factor VIII proteins or are packaged more efficiently into viral vectors.Type: GrantFiled: March 17, 2017Date of Patent: November 9, 2021Assignee: SPARK THERAPEUTICS, INC.Inventors: Xavier Anguela, Sam Hsien-I Shen
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Publication number: 20210222141Abstract: The invention provides nucleic acids encoding acid a-glucosidase (GAA). In certain embodiments, nucleic acids have greater than about 86% sequence identity to a sequence selected from the group consisting of any of the sequences set forth as SEQ ID NOs:1-5. In certain embodiments, nucleic acids encoding acid a-glucosidase (GAA) contain less than 127 CpG dinucleotides. Expression cassettes, vectors, cells and cell lines and methods of using such nucleic acids encoding acid a-glucosidase (GAA) are also provided.Type: ApplicationFiled: May 15, 2019Publication date: July 22, 2021Applicant: SPARK THERAPEUTICS, INC.Inventors: Xavier ANGUELA, Sean ARMOUR, Jayme NORDIN
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Publication number: 20210079422Abstract: Described and provided herein are purification, production and manufacturing methods for recombinant adeno-associated viral (rAAV) vector particles. Purification, production and manufacturing methods set forth herein, for example, include at least 2 column chromatography steps. Column chromatography steps include, for example, cation exchange chromatography, anion exchange chromatography, size exclusion chromatography and/or AAV affinity chromatography alone or in combination and in any order.Type: ApplicationFiled: June 29, 2018Publication date: March 18, 2021Applicant: Spark Therapeutics, Inc.Inventors: Younghoon OH, Guang QU
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Publication number: 20200299650Abstract: In accordance with the invention, provided herein are methods for purifying recombinant adeno-associated (rAAV) vector particles.Type: ApplicationFiled: March 31, 2017Publication date: September 24, 2020Applicant: SPARK THERAPEUTICS, INC.Inventors: Guang QU, Younghoon OH, Lin LU, John Fraser WRIGHT
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Publication number: 20200237930Abstract: Methods of using vvectors comprising nucleic acid and nucleic acid variants encoding FVIII protein are disclosed. In particular embodiments, a method of treating a human having hemophilia A includes administering a recombinant adeno-associated virus (rAAV) vector comprising a nucleic acid encoding Factor VIII (FVIII) or nucleic acid variant encoding Factor VIII (FVIII) having a B domain deletion (hFVIII-BDD). In some aspects, a nucleic acid variant has 95% or greater identity to SEQ ID NO:7 and/or a nucleic acid variant has no more than 2 cytosine-guanine dinucleotides (CpGs). In other aspects, a rAAV vector is administered to the human at a dose of less than about 6×1012 vector genomes per kilogram (vg/kg).Type: ApplicationFiled: August 1, 2018Publication date: July 30, 2020Applicant: SPARK THERAPEUTICS, INC.Inventor: Xavier ANGUELA
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Publication number: 20200164008Abstract: Provided are methods of treating a subject in need of treatment for a disease caused by a loss of function or activity of a protein. Also provided are methods of treating a subject in need of treatment for a disease caused by a gain of function, activity or expression, of a protein.Type: ApplicationFiled: July 17, 2018Publication date: May 28, 2020Applicant: SPARK THERAPEUTICS, INC.Inventors: John Fraser WRIGHT, Marcus Eugene CARR, JR.
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Publication number: 20200165632Abstract: Provided are compositions and methods of transducing/transfecting cells with a molecule, such as a nucleic acid (e.g., plasmid), at high efficiency. High efficiency transduced/transfected cells can, when transduced with a nucleic acid that encodes a protein or comprises a sequence that is transcribed into a transcript of interest, produce high amounts of protein and/or transcript. High efficiency transduced/transfected cells can, when transduced with plasmids comprising (i) nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins; and (ii) a transgene that encodes a protein or is transcribed into a transcript of interest; produce high amounts of recombinant rAAV vector.Type: ApplicationFiled: June 6, 2018Publication date: May 28, 2020Applicant: Spark Therapeutics, Inc.Inventors: Guang QU, Lin LU, Jesusa JOSUE-ALMQVIST, John Fraser WRIGHT
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Patent number: 10633689Abstract: Methods for measuring REP-1 and REP-2 activity are provided. In certain embodiments, a method includes: (a) contacting cells that do not express endogenous functional REP-1 or REP-2 protein with an adeno-associated viral (AAV) vector comprising a CHM gene encoding a REP-1 protein or CHM like gene encoding a REP-2 protein under conditions allowing cell transduction; (b) incubating transduced cells under conditions allowing expression of the encoded REP-1 or REP-2 protein; (c) lysing the transduced cells to produce an extract comprising the encoded REP-1 or REP-2 protein and Rab small GTPase (Rabs); (d) incubating said extract with a Rab substrate for a period of time and under conditions allowing prenylation of the Rab thereby forming prenylated Rab; and (e) detecting and/or quantifying the prenylated Rab, wherein the amount of prenylated Rab reflects REP-1 or REP-2 activity thereby measuring REP-1 or REP-2 activity.Type: GrantFiled: November 7, 2017Date of Patent: April 28, 2020Assignee: SPARK THERAPEUTICS, INC.Inventors: John Fraser Wright, Marina Sumaroka