US 12,280,122 B2
Muscle targeting complexes and uses thereof for treating myotonic dystrophy
Romesh R. Subramanian, Framingham, MA (US); Mohammed T. Qatanani, Waltham, MA (US); Timothy Weeden, Waltham, MA (US); and Cody A. Desjardins, Waltham, MA (US)
Assigned to Dyne Therapeutics, Inc., Waltham, MA (US)
Filed by Dyne Therapeutics, Inc., Waltham, MA (US)
Filed on Aug. 9, 2024, as Appl. No. 18/799,447.
Application 18/799,447 is a continuation of application No. 18/416,981, filed on Jan. 19, 2024, granted, now 12,097,263.
Application 18/416,981 is a continuation of application No. 17/205,102, filed on Mar. 18, 2021, granted, now 11,911,484.
Application 17/205,102 is a continuation of application No. 17/264,905, abandoned, previously published as PCT/US2019/044987, filed on Aug. 2, 2019.
Claims priority of provisional application 62/859,672, filed on Jun. 10, 2019.
Claims priority of provisional application 62/858,888, filed on Jun. 7, 2019.
Claims priority of provisional application 62/855,761, filed on May 31, 2019.
Claims priority of provisional application 62/779,161, filed on Dec. 13, 2018.
Claims priority of provisional application 62/713,914, filed on Aug. 2, 2018.
Prior Publication US 2024/0398967 A1, Dec. 5, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/68 (2017.01); A61K 47/60 (2017.01); A61P 21/00 (2006.01); C07K 16/28 (2006.01); C12N 15/113 (2010.01)
CPC A61K 47/6807 (2017.08) [A61K 47/60 (2017.08); A61K 47/6849 (2017.08); A61P 21/00 (2018.01); C07K 16/2881 (2013.01); C12N 15/1137 (2013.01); C07K 2317/55 (2013.01); C07K 2317/92 (2013.01); C12N 2310/11 (2013.01); C12N 2310/315 (2013.01); C12N 2310/322 (2013.01); C12N 2310/3513 (2013.01)] 24 Claims
 
1. A composition comprising a plurality of complexes, each complex comprising an anti-transferrin receptor antibody covalently linked, via a protease-sensitive linker, to an oligonucleotide that targets a DMPK RNA, wherein each complex is configured for delivering the oligonucleotide into muscle cells,
wherein the oligonucleotide is 15, 16, 17, or 18 nucleotides in length and comprises a region of complementarity that is fully complementary, along a length of at least 14 contiguous nucleotides, to a coding region of a DMPK sequence as set forth in SEQ ID NO: 15,
wherein the oligonucleotide is configured to bring about degradation of the DMPK RNA via RNase H mediated degradation, wherein the oligonucleotide comprises a 5′-X-Y-Z-3′ formula, wherein X and Z are flanking regions comprising one or more 2′-modified nucleosides selected from the group consisting of: 2′-O-methyl, 2′-fluoro, 2′-O-methoxyethyl, and 2′,4′-bridged nucleosides, wherein Y is a gap region and each nucleoside in Y is a 2′-deoxyribonucleoside, and wherein the oligonucleotide comprises one or more phosphorothioate internucleoside linkages; and
wherein the anti-transferrin receptor antibody binds an extracellular domain of a transferrin receptor protein 1 (TfR1).