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:
![]() 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.
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