US 11,986,537 B2
Muscle targeting complexes and uses thereof for treating dystrophinopathies
Romesh R. Subramanian, Framingham, MA (US); Mohammed T. Qatanani, Waltham, MA (US); Timothy Weeden, Waltham, MA (US); Cody A. Desjardins, Waltham, MA (US); Brendan Quinn, Waltham, MA (US); and John Najim, Waltham, MA (US)
Assigned to Dyne Therapeutics, Inc., Waltham, MA (US)
Filed by Dyne Therapeutics, Inc., Waltham, MA (US)
Filed on Jul. 10, 2023, as Appl. No. 18/349,631.
Application 18/349,631 is a continuation of application No. 17/811,370, filed on Jul. 8, 2022, granted, now 11,771,776.
Claims priority of provisional application 63/220,262, filed on Jul. 9, 2021.
Prior Publication US 2023/0346967 A1, Nov. 2, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01); A61K 47/68 (2017.01); A61P 21/00 (2006.01)
CPC A61K 47/6849 (2017.08) [A61K 47/6807 (2017.08); A61K 47/6889 (2017.08); A61P 21/00 (2018.01)] 19 Claims
 
1. A composition comprising complexes comprising an anti-transferrin receptor (TfR) antibody covalently linked to at least one oligonucleotide, wherein the antibody is a Fab and comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 101 and a light chain comprising the amino acid sequence of SEQ ID NO: 90, and wherein each anti-TfR antibody of the complexes is on average covalently linked to 1 to 3 oligonucleotides, and wherein the oligonucleotide induces dystrophin exon 53 skipping, wherein the complexes of the composition comprise a structure of:

OG Complex Work Unit Chemistry
wherein n is 3 and m is 4, wherein L1 comprises a spacer that is a substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, —O—, —N(RA)—, —S—, —C(═O)—, —C(═O)O—, —C(═O)NRA—, —NRAC(═O)—, —NRAC(═O)RA—, —C(═O)RA—, —NRAC(═O)O—, —NRAC(═O)N(RA)—, —OC(═O)—, —OC(═O)O—, —OC(═O)N(RA)—, —S(O)2NRA—, —NRAS(O)2—, or a combination thereof, wherein each RA is independently hydrogen or substituted or unsubstituted alkyl.