US 12,263,225 B2
Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and methods of use thereof to target dystrophin and to treat Duchenne muscular dystrophy
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 May 1, 2024, as Appl. No. 18/651,734.
Application 18/651,734 is a continuation of application No. 18/492,894, filed on Oct. 24, 2023, granted, now 12,005,124.
Application 18/492,894 is a continuation of application No. 18/181,623, filed on Mar. 10, 2023, granted, now 11,833,217.
Application 18/181,623 is a continuation of application No. 17/930,522, filed on Sep. 8, 2022, granted, now 11,633,496.
Application 17/930,522 is a continuation of application No. 17/751,875, filed on May 24, 2022, granted, now 11,497,815.
Application 17/751,875 is a continuation of application No. 17/580,844, filed on Jan. 21, 2022, granted, now 11,369,689.
Application 17/580,844 is a continuation of application No. 17/501,066, filed on Oct. 14, 2021, granted, now 11,248,056.
Application 17/501,066 is a continuation of application No. 17/205,151, filed on Mar. 18, 2021, granted, now 11,168,141.
Application 17/205,151 is a continuation of application No. 17/265,024, abandoned, previously published as PCT/US2019/044949, filed on Aug. 2, 2019.
Claims priority of provisional application 62/855,766, filed on May 31, 2019.
Claims priority of provisional application 62/714,031, filed on Aug. 2, 2018.
Prior Publication US 2024/0293568 A1, Sep. 5, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/68 (2017.01); A61K 39/00 (2006.01); A61K 47/10 (2017.01); A61K 47/54 (2017.01); A61P 21/00 (2006.01); C07K 16/28 (2006.01); C12N 15/113 (2010.01)
CPC A61K 47/6807 (2017.08) [A61K 47/10 (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 composition comprising complexes that comprise an anti-transferrin receptor antibody covalently linked to at least one 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 each oligonucleotide of the complexes 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 each oligonucleotide of the complexes is a phosphorodiamidate morpholino oligomer (PMO); and
wherein, for each complex, each oligonucleotide of the complex is independently covalently linked at its 5′ end to a lysine residue of the anti-transferrin receptor antibody of the complex via a cleavable linker comprising a valine-citrulline sequence.