US 12,012,460 B2
Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide
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. 15, 2023, as Appl. No. 18/467,851.
Application 18/467,851 is a continuation of application No. 18/184,905, filed on Mar. 16, 2023, granted, now 11,795,234.
Application 18/184,905 is a continuation of application No. 17/936,483, filed on Sep. 29, 2022, granted, now 11,787,869.
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, abandoned, 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 2024/0067743 A1, Feb. 29, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 47/68 (2017.01); A61P 21/00 (2006.01); C12N 15/113 (2010.01)
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)] 28 Claims
 
1. A complex comprising 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;
wherein the oligonucleotide comprises one or more modifications and 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: 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.