Complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and method of delivering an oligonucleotide to a subject
Romesh R. Subramanian, Framingham, MA (US); Mohammed T. Qatanani, Waltham, MA (US); Timothy Weeden, Waltham, MA (US); and Cody A. Desjardins, Waltham, MA (US)
Assigned to Dyne Therapeutics, Inc., Waltham, MA (US)
Filed by Dyne Therapeutics, Inc., Waltham, MA (US)
Filed on Apr. 24, 2025, as Appl. No. 19/189,163.
Application 19/189,163 is a continuation of application No. 18/939,894, filed on Nov. 7, 2024, granted, now 12,319,743.
Application 18/939,894 is a continuation of application No. 18/656,654, filed on May 7, 2024, granted, now 12,173,078.
Application 18/656,654 is a continuation of application No. 18/468,580, filed on Sep. 15, 2023, granted, now 12,018,087.
Application 18/468,580 is a continuation in part of application No. 18/184,741, filed on Mar. 16, 2023, granted, now 11,795,233.
Application 18/184,741 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 18/468,580 is a continuation in part of application No. 17/265,019, abandoned, previously published as PCT/US2019/044959, filed on Aug. 2, 2019.
Application 18/468,580 is a continuation in part of application No. 17/264,972, abandoned, previously published as PCT/US2019/044961, filed on Aug. 2, 2019.
Application 18/468,580 is a continuation in part of application No. 17/264,998, abandoned, previously published as PCT/US2019/044982, filed on Aug. 2, 2019.
Application 18/468,580 is a continuation in part of application No. 17/264,905, abandoned, previously published as PCT/US2019/044987, filed on Aug. 2, 2019.
Application 18/468,580 is a continuation in part of application No. 17/265,024, abandoned, previously published as PCT/US2019/044949, filed on Aug. 2, 2019.
Application 18/468,580 is a continuation in part of application No. 17/265,044, abandoned, previously published as PCT/US2019/044955, filed on Aug. 2, 2019.
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.
Application 18/468,580 is a continuation in part of application No. 17/265,016, abandoned, previously published as PCT/US2019/044960, filed on Aug. 2, 2019.
Claims priority of provisional application 62/859,694, filed on Jun. 10, 2019.
Claims priority of provisional application 62/859,672, filed on Jun. 10, 2019.
Claims priority of provisional application 62/858,888, filed on Jun. 7, 2019.
Claims priority of provisional application 62/858,925, filed on Jun. 7, 2019.
Claims priority of provisional application 62/855,761, filed on May 31, 2019.
Claims priority of provisional application 62/855,781, filed on May 31, 2019.
Claims priority of provisional application 62/855,766, filed on May 31, 2019.
Claims priority of provisional application 62/779,173, filed on Dec. 13, 2018.
Claims priority of provisional application 62/779,161, filed on Dec. 13, 2018.
Claims priority of provisional application 62/714,031, filed on Aug. 2, 2018.
Claims priority of provisional application 62/713,959, filed on Aug. 2, 2018.
Claims priority of provisional application 62/713,933, filed on Aug. 2, 2018.
Claims priority of provisional application 62/714,035, filed on Aug. 2, 2018.
Claims priority of provisional application 62/713,914, filed on Aug. 2, 2018.
Claims priority of provisional application 62/714,010, filed on Aug. 2, 2018.
Claims priority of provisional application 62/714,034, filed on Aug. 2, 2018.
Claims priority of provisional application 62/714,025, filed on Aug. 2, 2018.
Prior Publication US 2025/0304710 A1, Oct. 2, 2025
1. A complex comprising an anti-transferrin receptor antibody covalently linked to a 5′ end or a 3′ end of an oligonucleotide via a linker,
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 comprises an antisense strand comprising a region of complementarity of at least 15 nucleotides in length to the nucleotide sequence as set forth in SEQ ID NO: 15, wherein the oligonucleotide is in the range of 19-25 nucleotides in length;
wherein the one or more modifications comprise a 2′-modified nucleoside selected from the group consisting of: a 2′-O-methyl nucleoside, a 2′-fluoro nucleoside, and combinations thereof, and comprise a modified backbone comprising one or more phosphorothioate linkages,
wherein the complex is formable by a process comprising reacting a first electrophile of a linker precursor compound and a thiol group of a cysteine of the anti-transferrin receptor antibody.