US 12,286,630 B2
Treatment methods for muscular dystrophy
Huadong Sun, Cambridge, MA (US); Lilly East, Cambridge, MA (US); Jon Tinsley, Cambridge, MA (US); and Jake Elkins, Cambridge, MA (US)
Assigned to Sarepta Therapeutics, Inc., Cambridge, MA (US)
Filed by Sarepta Therapeutics, Inc., Cambridge, MA (US)
Filed on Apr. 29, 2022, as Appl. No. 17/732,757.
Claims priority of provisional application 63/182,327, filed on Apr. 30, 2021.
Claims priority of provisional application 63/249,721, filed on Sep. 29, 2021.
Prior Publication US 2023/0193282 A1, Jun. 22, 2023
Int. Cl. C12N 15/11 (2006.01); A61P 21/00 (2006.01); C12N 15/113 (2010.01)
CPC C12N 15/1138 (2013.01) [A61P 21/00 (2018.01); C12N 15/113 (2013.01); C12N 2310/11 (2013.01); C12N 2310/3233 (2013.01)] 22 Claims
 
1. A method of treating a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation that is amenable to exon skipping, comprising administering to the patient an antisense oligomer conjugate of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein:
n is 1-40;
each Nu is a nucleobase, which, taken together, form a targeting sequence complementary to an exon annealing site in the dystrophin pre-mRNA;
T′ is a moiety selected from:

OG Complex Work Unit Chemistry
wherein
R100 a cell-penetrating peptide, R200 is hydrogen, and R1 is C1-C6 alkyl,
at a dose equivalent to the dose of the 6HCl salt of the conjugate according to the following schedule:
i) about 300 mg to about 700 mg, or about 900 mg to about 1200 mg, once every four weeks for a patient that weighs from about 10 kg to about 25 kg;
ii) about 600 mg to about 800 mg, or about 1000 mg to about 1300 mg, once every four weeks for a patient that weighs from about 25 kg to about 50 kg; or
iii) about 700 mg to about 900 mg, or about 1200 mg to about 1500 mg, once every four weeks for a patient that weighs from about 50 kg to about 100 kg;
to achieve a mean AUC
about 100 and about 200 ug·h/mL, or is between about 200 and about 500 ug·h/mL, and
wherein the method further comprises administering a magnesium supplement to the patient.