CPC A61K 47/6807 (2017.08) [A61K 47/10 (2013.01); A61K 47/549 (2017.08); A61K 47/6849 (2017.08); A61P 21/00 (2018.01); C07K 16/2881 (2013.01); C12N 15/113 (2013.01); C12N 15/1137 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/33 (2013.01); C07K 2317/55 (2013.01); C07K 2317/77 (2013.01); C07K 2317/92 (2013.01); C12N 2310/11 (2013.01); C12N 2310/14 (2013.01); C12N 2310/315 (2013.01); C12N 2310/3233 (2013.01); C12N 2310/3513 (2013.01); C12N 2320/32 (2013.01)] | 30 Claims |
1. A complex comprising an anti-transferrin receptor antibody covalently linked to an exon-skipping oligonucleotide,
wherein the anti-transferrin receptor antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and the light chain variable region comprise human or humanized framework regions; 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 of the complex is 30 nucleotides in length and comprises a region of complementarity of 25, 26, 27, 28, 29, or 30 nucleotides in length, wherein the region of complementarity is complementary to the annealing site of an oligonucleotide consisting of the sequence of SEQ ID NO: 195, wherein the oligonucleotide of the complex is a phosphorodiamidate morpholino oligomer (PMO); and
wherein the oligonucleotide of the complex is covalently linked at the 5′ end to a lysine residue of the anti-transferrin receptor antibody via a cleavable linker comprising a valine-citrulline sequence.
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