公开(公告)号：US20200299650A1

公开(公告)日：2020-09-24

申请号：US16088743

申请日：2017-03-31

Applicant: SPARK THERAPEUTICS, INC.

Inventor： Guang QU ,  Younghoon OH ,  Lin LU ,  John Fraser WRIGHT

IPC: C12N7/00 ,  C12N1/06 ,  B01D15/36 ,  B01D15/34 ,  B01D61/14 ,  B01D15/38

Abstract: In accordance with the invention, provided herein are methods for purifying recombinant adeno-associated (rAAV) vector particles.

公开(公告)号：US20200165632A1

公开(公告)日：2020-05-28

申请号：US16619898

申请日：2018-06-06

Applicant: Spark Therapeutics, Inc.

Inventor： Guang QU ,  Lin LU ,  Jesusa JOSUE-ALMQVIST ,  John Fraser WRIGHT

IPC: C12N15/87 ,  C12N5/073

Abstract: 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.

公开(公告)号：US20190284576A1

公开(公告)日：2019-09-19

申请号：US16319216

申请日：2017-07-21

Applicant: Spark Therapeutics, Inc.

Inventor： Guang QU ,  John Fraser WRIGHT ,  Younghoon OH ,  Yuhuan WANG ,  Haibo ZHANG ,  Laura DUNCAN

IPC: C12N15/86 ,  C07K14/755 ,  C12N9/64 ,  C12N9/48

Abstract: Provided are methods for producing recombinant adeno-associated virus (rAAV) vector particles at high recovery or high titer. Also provided are methods that concentrate rAAV vectors to a high concentration, for example, up to 5E+13 (5×1013) vector genomes per milliliter (Vg/ml) with little if any rAAV aggregates.

公开(公告)号：US20250073353A1

公开(公告)日：2025-03-06

申请号：US18803700

申请日：2024-08-13

Applicant: SPARK THERAPEUTICS, INC.

Inventor： Xavier ANGUELA

IPC: A61K48/00 ,  A61K9/51 ,  A61K38/37 ,  A61P7/02 ,  C12N15/86

Abstract: Methods of using vectors 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).

公开(公告)号：US20240350667A1

公开(公告)日：2024-10-24

申请号：US18685681

申请日：2022-07-22

Applicant: Spark Therapeutics, Inc.

Inventor： Xavier Anguel ,  Pedro Cejas ,  Ali Nahvi ,  Mustafa Yazicioglu, III ,  Rui Zhang

IPC: A61K48/00 ,  A61K9/127 ,  A61K9/51 ,  A61K31/404 ,  A61K31/437 ,  A61K45/06 ,  C12N15/88

CPC classification number: A61K48/005 ,  A61K9/127 ,  A61K9/5123 ,  A61K31/404 ,  A61K31/437 ,  A61K45/06 ,  A61K48/0083 ,  C12N15/88

Abstract: The present invention features method and composition that can be used to facilitate intracellular delivery of DNA to a subject. The provided methods and compositions employ a nanoparticle for intracellular DNA delivery and a cytosolic DNA-sensing inhibitor. The cytosolic DNA-sensing inhibitor is provided to decrease the subject's immune response that can be stimulated by the DNA.

公开(公告)号：US20230142731A1

公开(公告)日：2023-05-11

申请号：US17862622

申请日：2022-07-12

Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  GENETHON ,  SORBONNE UNIVERSITÉ ,  UNIVERSITÉ DE PARIS ,  SPARK THERAPEUTICS, INC.

Inventor： Sébastien LACROIX-DESMAZES ,  Federico MINGOZZI ,  Jordan DIMITROV ,  Christian LEBORGNE ,  Sean ARMOUR

IPC: A61K48/00 ,  C12N9/24 ,  C12N15/113 ,  C12N15/86 ,  A61K38/48 ,  C12N9/64 ,  C12N15/861

CPC classification number: A61K48/005 ,  C12N9/2402 ,  C12N15/113 ,  C12N15/86 ,  A61K38/4873 ,  C12N9/6475 ,  C12N15/861 ,  C12N2310/11 ,  C12N2310/141 ,  C12N2750/14143 ,  C12Y302/01 ,  C12Y304/22 ,  C12Y304/2201 ,  G01N33/6854

Abstract: Disclosed herein are methods for treating patients that may develop or already have pre-existing gene therapy neutralizing antibodies by administering a protease that cleaves peptide bonds present in immunoglobulins or by administering a glycosidase that cleaves carbohydrate residues present on immunoglobulins, or other similar enzymatic cleavage of immunoglobulins in vivo. Also disclosed are methods for utilizing IdeS and other immunoglobulin G-degrading enzyme polypeptides for gene therapy treatment of a disease in a patient in need thereof.

公开(公告)号：US20190038724A1

公开(公告)日：2019-02-07

申请号：US16156649

申请日：2018-10-10

Applicant: SPARK THERAPEUTICS, INC.

Inventor： George Buchlis ,  Xavier Anguela ,  Katherine A. High

IPC: A61K38/46 ,  C12N15/10 ,  C12N9/22 ,  A61K31/7088

Abstract: 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.

公开(公告)号：US20180135097A1

公开(公告)日：2018-05-17

申请号：US15806136

申请日：2017-11-07

Applicant: Spark Therapeutics, Inc.

Inventor： John Fraser WRIGHT ,  Marina SUMAROKA

IPC: C12Q1/48

CPC classification number: C12Q1/48 ,  C12Y205/0106 ,  G01N2333/91171

Abstract: 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.

公开(公告)号：US20250101396A1

公开(公告)日：2025-03-27

申请号：US18828493

申请日：2024-09-09

Applicant: Spark Therapeutics, Inc.

Inventor： Xavier Anguela ,  Sean Armour ,  Jayme Nordin

IPC: C12N9/26 ,  A61K48/00 ,  C12N15/86

Abstract: The invention provides nucleic acids encoding acid α-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 α-glucosidase (GAA) contain less than 127 CpG dinucleotides. Expression cassettes, vectors, cells and cell lines and methods of using such nucleic acids encoding acid α-glucosidase (GAA) are also provided.

公开(公告)号：US20240301380A1

公开(公告)日：2024-09-12

申请号：US18261285

申请日：2022-01-13

Applicant: Spark Therapeutics, Inc.

Inventor： Sean Armour ,  Daniel Cohen ,  Christopher Riling

IPC: C12N9/40 ,  A61K48/00 ,  A61P3/00 ,  C12N15/86

CPC classification number: C12N9/2465 ,  A61K48/0058 ,  A61P3/00 ,  C12N15/86 ,  C07K2319/02 ,  C12N2750/14143 ,  C12N2830/008 ,  C12N2830/15 ,  C12N2830/42 ,  C12N2830/50 ,  C12Y302/01022

Abstract: Polynucleotides including nucleic acids encoding α-galactosidase A (GLA) are described. Also described are expression cassettes, vectors, cells, and cell lines containing the polynucleotides, as well as methods of using the polynucleotides to treat lysosomal storage disorders such as Fabry disease.