公开(公告)号：US20240074986A1

公开(公告)日：2024-03-07

申请号：US18258981

申请日：2021-12-22

Applicant: Spark Therapeutics, Inc.

Inventor： Ali Nahvi ,  Xavier Anguela ,  Rui Zhang

IPC: A61K9/51 ,  A61K31/573 ,  A61K31/663 ,  A61K48/00 ,  C07K16/28 ,  C12N15/88

CPC classification number: A61K9/5123 ,  A61K31/573 ,  A61K31/663 ,  A61K48/0058 ,  C07K16/2866 ,  C12N15/88

Abstract: Methods of delivering a transgene to a subject in need thereof are described. In particular, the methods include administering to the subject (i) a phagocyte-depleting agent, and (ii) a pharmaceutical composition comprising a non-viral vector comprising the transgene and a pharmaceutically acceptable carrier. The methods can be used to treat a subject in need of treatment for a disease caused by a loss of function or activity of a protein, or to treat a subject in need of treatment for a disease caused by a gain of function activity or expression of a protein.

公开(公告)号：US20230241247A1

公开(公告)日：2023-08-03

申请号：US17759183

申请日：2021-01-22

Applicant: SPARK THERAPEUTICS, INC.

Inventor： Sean ARMOUR

IPC: A61K48/00 ,  C07K16/28 ,  A61K38/48 ,  A61K38/47 ,  A61K38/46 ,  A61K31/7088 ,  C12N15/86 ,  C12N15/11 ,  C12N9/22 ,  G01N33/569

CPC classification number: A61K48/0041 ,  C07K16/283 ,  A61K38/48 ,  A61K38/47 ,  A61K48/0083 ,  A61K38/465 ,  A61K31/7088 ,  C12N15/86 ,  C12N15/11 ,  C12N9/22 ,  G01N33/56983 ,  C12N2310/20 ,  C12N2800/80 ,  C12N2750/14143 ,  C12N2750/14145 ,  C12N2750/14171 ,  G01N2469/20

Abstract: 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.

公开(公告)号：US20230040275A1

公开(公告)日：2023-02-09

申请号：US17777954

申请日：2020-11-19

Applicant: SPARK THERAPEUTICS, INC.

Inventor： David William ANDERSON ,  Brittney L. GURDA ,  Federico MINGOZZI ,  Mustafa N. YAZICIOGLU ,  William QUINN

IPC: C12N15/62 ,  A61K39/35 ,  A61K39/00 ,  C07K14/705 ,  C12N15/86 ,  A61K48/00 ,  A61P37/06 ,  A61K31/436 ,  C07K14/47 ,  C07K14/005

Abstract: 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.

公开(公告)号：US20220184188A1

公开(公告)日：2022-06-16

申请号：US17310378

申请日：2020-01-31

Applicant: SPARK THERAPEUTICS, INC.

Inventor： David William ANDERSON ,  Maryann TOTO ,  Sue E.I. DASEN

IPC: A61K38/48 ,  A61K48/00 ,  A61P37/06 ,  C12N15/86

Abstract: 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.

公开(公告)号：US20220025396A1

公开(公告)日：2022-01-27

申请号：US17052097

申请日：2019-05-07

Applicant: Spark Therapeutics, Inc.

Inventor： Guang QU ,  Denis PHICHITH ,  Jingmin ZHOU

IPC: C12N15/86

Abstract: 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.

公开(公告)号：US20210363192A1

公开(公告)日：2021-11-25

申请号：US17050362

申请日：2019-04-26

Applicant: SPARK THERAPEUTICS, INC.

Inventor： Xavier ANGUELA ,  Sean ARMOUR ,  Nicholas KEISER ,  Suryanarayan SOMANATHAN ,  Mustafa N. YAZICIOGLU

IPC: C07K14/005 ,  C12N7/00 ,  C12N15/86 ,  C12N15/113

Abstract: 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.

公开(公告)号：US20210348210A1

公开(公告)日：2021-11-11

申请号：US16096673

申请日：2017-04-28

Applicant: SPARK THERAPEUTICS, INC.

Inventor： Linda COUTO

IPC: C12Q1/34 ,  B01D15/38 ,  B01D15/32

Abstract: Methods for assaying function and/or activity and/or potency of isomerohydrolase proteins are provided.

公开(公告)号：US11168124B2

公开(公告)日：2021-11-09

申请号：US15462660

申请日：2017-03-17

Applicant: SPARK THERAPEUTICS, INC.

Inventor： Xavier Anguela ,  Sam Hsien-I Shen

IPC: C12N15/86 ,  C07K14/755 ,  A61K38/37 ,  A61K45/06 ,  A61K48/00 ,  C12N7/00

Abstract: 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.

公开(公告)号：US20210079422A1

公开(公告)日：2021-03-18

申请号：US16627227

申请日：2018-06-29

Applicant: Spark Therapeutics, Inc.

Inventor： Younghoon OH ,  Guang QU

IPC: C12N15/86 ,  B01D15/34 ,  B01D15/36

Abstract: 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.

公开(公告)号：US20200237930A1

公开(公告)日：2020-07-30

申请号：US16635957

申请日：2018-08-01

Applicant: SPARK THERAPEUTICS, INC.

Inventor： Xavier ANGUELA

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

Abstract: 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).