Treatment methods for muscular dystrophy
AssigneeSarepta Therapeutics, Inc.
InventorsHuadong Sun, Lilly East, Jon Tinsley, Jake Elkins
Life of this patent
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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.
Claims22
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):
- 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:
- 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.
A method of treating a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation that is amenable to exon 51 skipping, comprising administering to the patient an antisense oligomer conjugate of Formula (I):
- 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:
- 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 between about 200 and about 500 ug·h/mL, and
- wherein the method further comprises administering a magnesium supplement to the patient.
Dependencies are inferred from the claim text.