Compositions and methods for detection of smn protein in a subject and treatment of a subject
AssigneeBiogen MA Inc.
InventorsFrank Rigo, Katherine M. Bishop
Life of this patent
Estimating the term…
Abstract
Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy. Also provided are kits for detecting the amount of SMN protein in a sample of cerebrospinal fluid.
Claims140
A method of determining the amount of SMN protein in a biological sample comprising:
- a. collecting a biological sample from a human subject;
- b. contacting the biological sample with a capture antibody;
- c. contacting the biological sample with a detection antibody;
- d. measuring the amount of detection antibody in the biological sample;
- and
- calculating the amount of SMN protein in the biological sample.
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A kit for detecting the amount of SMN protein in a sample of cerebrospinal fluid comprising:
- a. a capture antibody labeled with a magnetic microparticle;
- b. a detection antibody labeled with a fluorophore.
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A kit for detecting the amount of SMN protein in a sample of cerebrospinal fluid comprising:
- a. a capture antibody labeled with a magnetic microparticle configured to bind with high specificity to an SMN protein;
- b. a detection antibody labeled with a fluorophore configured to bind with high specificity to an SMN protein;
- c. a device configured to detect the detection antibody labeled with a fluorophore and to calculate the concentration of SMN protein in the sample of cerebrospinal fluid.
A method for treating a human subject having one or more symptoms associated with spinal muscular atrophy (SMA), the method comprising administering by intrathecal injection doses of an antisense compound comprising an antisense oligonucleotide consisting of 18 linked nucleosides, wherein the oligonucleotide has a nucleobase sequence consisting of the nucleobase sequence SEQ ID NO:
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′-MOE nucleoside, and wherein each cytosine of the oligonucleotide is a 5-methyl cytosine, wherein the doses comprise:
- (i) a first dose of 12 mg of the antisense compound;
- (ii) a second dose of 12 mg of the antisense compound 12-18 days after administration of the first dose;
- (iii) a third dose of 12 mg of the antisense compound 25-35 days after administration of the first dose;
- (iv) a fourth dose of 12 mg of the antisense compound 60-70 days after administration of the first dose;
- and
- (v) a fifth dose of 12 mg of the antisense compound 178-188 days after administration of the first dose.
Dependencies are inferred from the claim text.