US 11,787,869 B2
Methods of using muscle targeting complexes to deliver an oligonucleotide to a subject having facioscapulohumeral muscular dystrophy or a disease associated with muscle weakness
Romesh R. Subramanian, Framingham, MA (US); Mohammed T. Qatanani, Waltham, MA (US); and Timothy Weeden, Waltham, MA (US)
Assigned to Dyne Therapeutics, Inc., Waltham, MA (US)
Filed by Dyne Therapeutics, Inc., Waltham, MA (US)
Filed on Sep. 29, 2022, as Appl. No. 17/936,483.
Application 17/936,483 is a continuation of application No. 17/846,738, filed on Jun. 22, 2022, granted, now 11,518,816.
Application 17/846,738 is a continuation of application No. 17/671,707, filed on Feb. 15, 2022, granted, now 11,390,682.
Application 17/671,707 is a continuation of application No. 17/400,295, filed on Aug. 12, 2021, granted, now 11,286,305.
Application 17/400,295 is a continuation of application No. 17/205,123, filed on Mar. 18, 2021, granted, now 11,111,309.
Application 17/205,123 is a continuation of application No. 17/264,948, previously published as PCT/US2019/044990, filed on Aug. 2, 2019.
Claims priority of provisional application 62/713,933, filed on Aug. 2, 2018.
Prior Publication US 2023/0049450 A1, Feb. 16, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); C12N 15/113 (2010.01); A61K 47/68 (2017.01); A61P 21/00 (2006.01)
CPC C07K 16/2881 (2013.01) [A61K 47/6807 (2017.08); A61K 47/6849 (2017.08); A61K 47/6889 (2017.08); A61P 21/00 (2018.01); C12N 15/113 (2013.01); C07K 2317/55 (2013.01); C07K 2317/92 (2013.01)] 30 Claims
 
1. A method of delivering an oligonucleotide to a subject, wherein the subject has facioscapulohumeral muscular dystrophy, the method comprising intravenously administering to the subject a complex that comprises an anti-transferrin receptor antibody covalently linked to a 5′ end or a 3′ end of an oligonucleotide,
wherein the anti-transferrin receptor antibody binds in the range of C89 to F760 of human transferrin receptor protein 1 (TfR1) having an amino acid sequence as set forth in SEQ ID NO: 1 and wherein the anti-transferrin receptor antibody does not specifically bind to the transferrin binding site of TfR1;
wherein the oligonucleotide comprises one or more modifications and a single strand that comprises a region of complementarity of at least 15 nucleotides in length to the nucleotide sequence as set forth in SEQ ID NO: 52, wherein the oligonucleotide is in the range of 15-30 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, and combinations thereof, and/or comprise a modified backbone selected from a backbone comprising one or more phosphorothioate linkages, a phosphorodiamidate morpholino backbone, and a peptide nucleic acid (PNA) backbone.