Abstract: Described herein are methods of treating muscular dystrophy comprising administering to a subject a recombinant AAV (rAAV) scAAVrh74.MHCK7.hSGCG vector, methods of expressing gamma-sarcoglycan gene in a patient, pharmaceutical compositions comprising the rAAV scAAVrh74.MHCK7.hSGCG for usage in such methods, the doses and the ranges thereof for such methods, and methods of generating and producing the rAAV scAAVrh74.MHCK7.hSGCG.
Abstract: The present disclosure relates to antisense oligomers and related compositions and methods for increasing the expression of functional human type VII collagen and methods for treating dystrophic epidermolysis bullosa and related disorders and relates to inducing exclusion of exon 80 in human type VII collagen mRNA.
Abstract: The disclosure is directed to a method for seed train expansion of adherent cells comprising culturing cells with a serum-supplemented growth medium in a N-2 vessel; removing the cells from the serum-supplemented medium; inoculating the cells from step into a serum-free growth medium in a N-1 vessel; culturing the cells in the N-1 vessel under suspension conditions; and inoculating a growth medium in a bioreactor with the suspension-cultured cells. In some aspects, the adherent cells are not suspension-adapted. In some aspects, the adherent cells are suspension-adapted. In some aspects, the adherent cells produced by the seed train expansion method are used to produce viral vectors. In some aspects, the viral vectors are AAV vectors.
Abstract: A modified antisense oligonucleotide of about 10 to about 40 nucleobases is disclosed. The oligonucleotide comprises a targeting sequence having a region complementary to at least one string of three or more identical contiguous nucleobases in a target sequence, wherein the target sequence comprises at least one additional nucleobase compared to the region of the targeting sequence and the at least one additional nucleobase has no complementary nucleobase in the region of the targeting sequence, and wherein the targeting region complementary to the at least one string of three or more identical contiguous nucleobases is internal to the targeting sequence.
Type:
Application
Filed:
December 22, 2022
Publication date:
December 21, 2023
Applicant:
Sarepta Therapeutics, Inc.
Inventors:
Frederick J. SCHNELL, Baozhong CAI, Jason GATLIN, Patrick L. IVERSEN
Abstract: Provided are LMNA-targeted antisense oligonucleotides for reducing expression of one or more aberrantly spliced LMNA mRNA isoforms that encode progerin.
Type:
Grant
Filed:
September 17, 2020
Date of Patent:
October 31, 2023
Assignees:
Sarepta Therapeutics, Inc., The United States of America, as rep. by the Secretary, Dept. of Health and Human Services, The Progeria Research Foundation
Inventors:
Michael R. Erdos, Francis S. Collins, Kan Cao, Ryszard Kole, Richard Keith Bestwick, Leslie B. Gordon
Abstract: Oligonucleotide analogues conjugated to carrier peptides are provided. The disclosed compounds are useful for the treatment of various diseases, for example diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.
Abstract: Provided are methods to characterize the VP1, VP2 and VPS capsid proteins in an adeno-associated virus (AAV) particle using liquid chromatography mass spectrometry, and/or ultraviolet (UV)-visible spectroscopy. The methods generally include the steps of (a) subjecting an AAV particle to liquid chromatography to denature and then separate the VP1, VP2 and VPS capsid proteins, and (b) subjecting the separated VP1, VP2 and VPS capsid proteins produced in step (a) to UV and mass spectrometry to determine the ratio and masses of the VP1, VP2 and VPS capsid proteins in the AAV particle. In another aspect, the disclosure provides an AAV composition comprising a post-translation modification. The disclosure also provides methods for characterizing the purity of AAV compositions using liquid chromatography mass spectrometry.
Abstract: New dosing regimens for treating muscular dystrophy in a patient suffering from Duchenne muscular dystrophy (DMD) with an antisense oligonucleotide conjugate that causes skipping of an exon in the human dystrophin gene are described. Also described is a method of treating a patient with an antisense oligomer CPP conjugate and a magnesium supplement.
Type:
Application
Filed:
April 29, 2022
Publication date:
June 22, 2023
Applicant:
Sarepta Therapeutics, Inc.
Inventors:
Huadong SUN, Lilly EAST, Jon TINSLEY, Jake ELKINS
Abstract: Provided herein are oligonucleotides, peptides, and peptide-oligonucleotide-conjugates. Also provided herein are methods of treating a muscle disease, a viral infection, or a bacterial infection in a subject in need thereof, comprising administering to the subject oligonucleotides, peptides, and peptide-oligonucleotide-conjugates described herein.
Abstract: The invention provides for a method for selectively reducing the expression of a mutant mRNA and/or protein having an expanded nucleotide repeat relative to a wild-type mRNA, comprising contacting a cell with an antisense oligonucleotide of sufficient length and complementarity to the expanded nucleotide repeat. More particularly it relates to selectively reducing the expression of mutant Huntington protein associated with Huntington's disease. The antisense oligonucleotide comprising either a nucleotide or a repeated three nucleotide sequence as defined in the claims.
Type:
Grant
Filed:
July 18, 2018
Date of Patent:
June 13, 2023
Assignee:
Sarepta Therapeutics, Inc.
Inventors:
Peter Linsley, Brian James Leppert, Gunnar J. Hanson
Abstract: Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.
Type:
Application
Filed:
June 15, 2022
Publication date:
February 16, 2023
Applicant:
Sarepta Therapeutics, Inc.
Inventors:
Baozhong CAI, Mitchell MARTINI, Katie THOMAS, Ross SHIMABUKU
Abstract: The present disclosure provides, among other things, improved compositions and methods for treating muscular dystrophy. For example, the disclosure provides methods for treating Duchenne muscular dystrophy patients having a mutation in the DMD gene that is amenable to exon 53 skipping by administering an effective amount of golodirsen.
Abstract: A modified antisense oligonucleotide of about 10 to about 40 nucleobases is disclosed. The oligonucleotide comprises a targeting sequence having a region complementary to at least one string of three or more identical contiguous nucleobases in a target sequence, wherein the target sequence comprises at least one additional nucleobase compared to the region of the targeting sequence and the at least one additional nucleobase has no complementary nucleobase in the region of the targeting sequence, and wherein the targeting region complementary to the at least one string of three or more identical contiguous nucleobases is internal to the targeting sequence.
Type:
Grant
Filed:
October 18, 2018
Date of Patent:
January 17, 2023
Assignee:
SAREPTA THERAPEUTICS, INC.
Inventors:
Frederick J. Schnell, Baozhong Cai, Jason Gatlin, Patrick L. Iversen
Abstract: Improved compositions and methods for treating muscular dystrophy by administering antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping are described.