US 12,104,156 B2
Compositions and methods of treating facioscapulohumeral muscular dystrophy
Barbora Malecova, San Diego, CA (US); Rob Burke, Carlsbad, CA (US); David Sala Cano, San Diego, CA (US); and Beatrice Diana Darimont, San Diego, CA (US)
Assigned to AVIDITY BIOSCIENCES, INC., San Diego, CA (US)
Filed by Avidity Biosciences, Inc., San Diego, CA (US)
Filed on Nov. 4, 2022, as Appl. No. 18/052,899.
Application 18/052,899 is a continuation of application No. 17/200,661, filed on Mar. 12, 2021, granted, now 11,525,137.
Claims priority of provisional application 63/066,655, filed on Aug. 17, 2020.
Claims priority of provisional application 62/992,071, filed on Mar. 19, 2020.
Prior Publication US 2023/0287420 A1, Sep. 14, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/113 (2010.01); A61K 31/7125 (2006.01); A61K 47/68 (2017.01); A61K 48/00 (2006.01); A61P 21/00 (2006.01); A61P 21/06 (2006.01); C07K 16/28 (2006.01); C07K 19/00 (2006.01)
CPC C12N 15/113 (2013.01) [A61K 31/7125 (2013.01); A61K 47/6807 (2017.08); A61K 47/6849 (2017.08); A61K 47/6889 (2017.08); A61K 48/005 (2013.01); A61P 21/00 (2018.01); A61P 21/06 (2018.01); C07K 16/2881 (2013.01); C07K 19/00 (2013.01); C07K 2317/55 (2013.01); C12N 2310/11 (2013.01); C12N 2310/14 (2013.01); C12N 2310/31 (2013.01); C12N 2310/313 (2013.01); C12N 2310/321 (2013.01); C12N 2310/3231 (2013.01); C12N 2310/3513 (2013.01); C12N 2320/32 (2013.01)] 16 Claims
 
1. A method of delivering an oligonucleotide to a subject, wherein the subject has facioscapulohumeral muscular dystrophy (FSHD), the method comprising intravenously administering to the subject a conjugate that comprises an anti-transferrin receptor antibody covalently linked to a 5′ end or a 3′ end of an oligonucleotide, wherein the oligonucleotide comprises one or more modifications and a strand that comprises a region of complementarity of at least 15 nucleotides in length to the nucleotide sequence of DUX4 mRNA;
wherein the oligonucleotide is in the range of 15-35 nucleotides in length; wherein the one or more modifications comprise a 2′-modified nucleoside selected from the group consisting of a 2′-O-methyl nucleoside, a 2′-fluoro nucleoside, a 2′-O-methoxyethyl nucleoside, and 2′,4′-bridged nucleosides, and combinations thereof, and/or comprise a modified backbone selected from a backbone comprising one or more phosphorothioate linkages and a phosphorodiamidate morpholino backbone; and
wherein the oligonucleotide brings about degradation of DUX4 mRNA as measured by the decreased expression of DUX4 biomarker RNAs comprising ZSCAN4 and LEUTX in the muscle cell.