Claims for Patent: 9,926,559

Summary for Patent: 9,926,559

Title:	Compositions and methods for modulation of SMN2 splicing in a subject
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.
Inventor(s):	Bennett; C. Frank (Carlsbad, CA), Hung; Gene (San Diego, CA), Rigo; Frank (Carlsbad, CA)
Assignee:	Biogen MA Inc. (Cambridge, MA)
Application Number:	14/760,171
Patent Claims:	1. A method of treating a human subject having spinal muscular atrophy (SMA), the method comprising administering to the human subject 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 antisense oligonucleotide is administered into the cerebrospinal fluid by bolus injection into the intrathecal space at a dose of 9.6, 10.3, 10.8, 11.3, or 12.0 milligrams of the antisense oligonucleotide. 2. The method of claim 1, wherein the administration is through a 21, 22, 23, 24, or 25 gauge needle. 3. The method of claim 1, wherein the administration is through a 22 gauge needle. 4. The method of claim 1, wherein the administration is between the L3 and L4 vertebrae. 5. The method of claim 1, wherein a 9.6 mg dose of the antisense oligonucleotide is administered in a volume of 4 mL, and wherein the dose is administered to the subject within 3 months of birth of the subject. 6. The method of claim 1, wherein a 10.3 mg dose of the antisense oligonucleotide is administered in a volume of 4.3 mL, and wherein the dose is administered to the subject between 3 and 6 months of birth of the subject. 7. The method of claim 1, wherein a 10.8 mg dose of the antisense oligonucleotide is administered in a volume of 4.5 mL, and wherein the dose is administered to the subject between 6 months and 12 months of birth of the subject. 8. The method of claim 1, wherein a 11.3 mg dose of the antisense oligonucleotide is administered in a volume of 4.7 mL, and wherein the dose is administered to the subject between 12 months and 24 months of birth of the subject. 9. The method of claim 1, wherein a 12.0 mg dose of the antisense oligonucleotide is administered in a volume of 5 mL, and wherein the dose is administered to the subject after 24 months of birth of the subject. 10. The method of claim 1, comprising administering to the human subject at least two doses wherein the second dose is administered 12-18 days after the first dose.